Datasets:

bigbio

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genia_term_corpus

like 2

[ { "id": "1", "type": "title", "text": [ "IL-2 gene expression and NF-kappa B activation through CD28 requires reactive oxygen production by 5-lipoxygenase." ], "offsets": [ [ 0, 114 ] ] }, { "id": "2", "type": "abstract", "text": [ "Activation of the CD28 surface receptor provides a major costimulatory signal for T cell activation resulting in enhanced production of interleukin-2 (IL-2) and cell proliferation. In primary T lymphocytes we show that CD28 ligation leads to the rapid intracellular formation of reactive oxygen intermediates (ROIs) which are required for CD28-mediated activation of the NF-kappa B/CD28-responsive complex and IL-2 expression. Delineation of the CD28 signaling cascade was found to involve protein tyrosine kinase activity, followed by the activation of phospholipase A2 and 5-lipoxygenase. Our data suggest that lipoxygenase metabolites activate ROI formation which then induce IL-2 expression via NF-kappa B activation. These findings should be useful for therapeutic strategies and the development of immunosuppressants targeting the CD28 costimulatory pathway." ], "offsets": [ [ 115, 979 ] ] } ]

[ { "id": "3", "type": "other_name", "text": [ "IL-2 gene expression" ], "offsets": [ [ 0, 20 ] ], "normalized": [] }, { "id": "4", "type": "DNA_domain_or_region", "text": [ "IL-2 gene" ], "offsets": [ [ 0, 9 ] ], "normalized": [] }, { "id": "5", "type": "other_name", "text": [ "NF-kappa B activation" ], "offsets": [ [ 25, 46 ] ], "normalized": [] }, { "id": "6", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 25, 35 ] ], "normalized": [] }, { "id": "7", "type": "protein_molecule", "text": [ "CD28" ], "offsets": [ [ 55, 59 ] ], "normalized": [] }, { "id": "8", "type": "protein_molecule", "text": [ "5-lipoxygenase" ], "offsets": [ [ 99, 113 ] ], "normalized": [] }, { "id": "9", "type": "protein_family_or_group", "text": [ "CD28 surface receptor" ], "offsets": [ [ 133, 154 ] ], "normalized": [] }, { "id": "10", "type": "protein_molecule", "text": [ "CD28" ], "offsets": [ [ 133, 137 ] ], "normalized": [] }, { "id": "11", "type": "other_name", "text": [ "T cell activation" ], "offsets": [ [ 197, 214 ] ], "normalized": [] }, { "id": "12", "type": "protein_molecule", "text": [ "interleukin-2" ], "offsets": [ [ 251, 264 ] ], "normalized": [] }, { "id": "13", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 266, 270 ] ], "normalized": [] }, { "id": "14", "type": "other_name", "text": [ "cell proliferation" ], "offsets": [ [ 276, 294 ] ], "normalized": [] }, { "id": "15", "type": "cell_type", "text": [ "primary T lymphocytes" ], "offsets": [ [ 299, 320 ] ], "normalized": [] }, { "id": "16", "type": "protein_molecule", "text": [ "CD28" ], "offsets": [ [ 334, 338 ] ], "normalized": [] }, { "id": "17", "type": "inorganic", "text": [ "reactive oxygen intermediates" ], "offsets": [ [ 394, 423 ] ], "normalized": [] }, { "id": "18", "type": "inorganic", "text": [ "ROIs" ], "offsets": [ [ 425, 429 ] ], "normalized": [] }, { "id": "19", "type": "other_name", "text": [ "CD28-mediated activation" ], "offsets": [ [ 454, 478 ] ], "normalized": [] }, { "id": "20", "type": "protein_molecule", "text": [ "CD28" ], "offsets": [ [ 454, 458 ] ], "normalized": [] }, { "id": "21", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 486, 496 ] ], "normalized": [] }, { "id": "22", "type": "protein_complex", "text": [ "CD28-responsive complex" ], "offsets": [ [ 497, 520 ] ], "normalized": [] }, { "id": "23", "type": "protein_molecule", "text": [ "CD28" ], "offsets": [ [ 497, 501 ] ], "normalized": [] }, { "id": "24", "type": "other_name", "text": [ "IL-2 expression" ], "offsets": [ [ 525, 540 ] ], "normalized": [] }, { "id": "25", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 525, 529 ] ], "normalized": [] }, { "id": "26", "type": "other_name", "text": [ "CD28 signaling cascade" ], "offsets": [ [ 561, 583 ] ], "normalized": [] }, { "id": "27", "type": "protein_molecule", "text": [ "CD28" ], "offsets": [ [ 561, 565 ] ], "normalized": [] }, { "id": "28", "type": "other_name", "text": [ "protein tyrosine kinase activity" ], "offsets": [ [ 605, 637 ] ], "normalized": [] }, { "id": "29", "type": "protein_family_or_group", "text": [ "protein tyrosine kinase" ], "offsets": [ [ 605, 628 ] ], "normalized": [] }, { "id": "30", "type": "protein_molecule", "text": [ "phospholipase A2" ], "offsets": [ [ 669, 685 ] ], "normalized": [] }, { "id": "31", "type": "protein_molecule", "text": [ "5-lipoxygenase" ], "offsets": [ [ 690, 704 ] ], "normalized": [] }, { "id": "32", "type": "protein_family_or_group", "text": [ "lipoxygenase metabolites" ], "offsets": [ [ 728, 752 ] ], "normalized": [] }, { "id": "33", "type": "protein_molecule", "text": [ "lipoxygenase" ], "offsets": [ [ 728, 740 ] ], "normalized": [] }, { "id": "34", "type": "other_name", "text": [ "ROI formation" ], "offsets": [ [ 762, 775 ] ], "normalized": [] }, { "id": "35", "type": "inorganic", "text": [ "ROI" ], "offsets": [ [ 762, 765 ] ], "normalized": [] }, { "id": "36", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 794, 798 ] ], "normalized": [] }, { "id": "37", "type": "other_name", "text": [ "NF-kappa B activation" ], "offsets": [ [ 814, 835 ] ], "normalized": [] }, { "id": "38", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 814, 824 ] ], "normalized": [] }, { "id": "39", "type": "other_name", "text": [ "therapeutic strategies" ], "offsets": [ [ 873, 895 ] ], "normalized": [] }, { "id": "40", "type": "other_name", "text": [ "immunosuppressants" ], "offsets": [ [ 919, 937 ] ], "normalized": [] }, { "id": "41", "type": "other_name", "text": [ "CD28 costimulatory pathway" ], "offsets": [ [ 952, 978 ] ], "normalized": [] }, { "id": "42", "type": "protein_molecule", "text": [ "CD28" ], "offsets": [ [ 952, 956 ] ], "normalized": [] } ]

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[ { "id": "44", "type": "title", "text": [ "The peri-kappa B site mediates human immunodeficiency virus type 2 enhancer activation in monocytes but not in T cells." ], "offsets": [ [ 0, 119 ] ] }, { "id": "45", "type": "abstract", "text": [ "Human immunodeficiency virus type 2 (HIV-2), like HIV-1, causes AIDS and is associated with AIDS cases primarily in West Africa. HIV-1 and HIV-2 display significant differences in nucleic acid sequence and in the natural history of clinical disease. Consistent with these differences, we have previously demonstrated that the enhancer/promoter region of HIV-2 functions quite differently from that of HIV-1. Whereas activation of the HIV-1 enhancer following T-cell stimulation is mediated largely through binding of the transcription factor NF-kappa B to two adjacent kappa B sites in the HIV-1 long terminal repeat, activation of the HIV-2 enhancer in monocytes and T cells is dependent on four cis-acting elements: a single kappa B site, two purine-rich binding sites, PuB1 and PuB2, and a pets site. We have now identified a novel cis-acting element within the HIV-2 enhancer, immediately upstream of the kappa B site, designated peri-kappa B. This site is conserved among isolates of HIV-2 and the closely related simian immunodeficiency virus, and transfection assays show this site to mediate HIV-2 enhancer activation following stimulation of monocytic but not T-cell lines. This is the first description of an HIV-2 enhancer element which displays such monocyte specificity, and no comparable enhancer element has been clearly defined for HIV-1. While a nuclear factor(s) from both peripheral blood monocytes and T cells binds the peri-kappa B site, electrophoretic mobility shift assays suggest that either a different protein binds to this site in monocytes versus T cells or that the protein recognizing this enhancer element undergoes differential modification in monocytes and T cells, thus supporting the transfection data. Further, while specific constitutive binding to the peri-kappa B site is seen in monocytes, stimulation with phorbol esters induces additional, specific binding. Understanding the monocyte-specific function of the peri-kappa B factor may ultimately provide insight into the different role monocytes and T cells play in HIV pathogenesis." ], "offsets": [ [ 120, 2195 ] ] } ]

[ { "id": "46", "type": "DNA_domain_or_region", "text": [ "peri-kappa B site" ], "offsets": [ [ 4, 21 ] ], "normalized": [] }, { "id": "47", "type": "other_name", "text": [ "human immunodeficiency virus type 2 enhancer activation" ], "offsets": [ [ 31, 86 ] ], "normalized": [] }, { "id": "48", "type": "DNA_domain_or_region", "text": [ "human immunodeficiency virus type 2 enhancer" ], "offsets": [ [ 31, 75 ] ], "normalized": [] }, { "id": "49", "type": "virus", "text": [ "human immunodeficiency virus type 2" ], "offsets": [ [ 31, 66 ] ], "normalized": [] }, { "id": "50", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 90, 99 ] ], "normalized": [] }, { "id": "51", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 111, 118 ] ], "normalized": [] }, { "id": "52", "type": "virus", "text": [ "Human immunodeficiency virus type 2" ], "offsets": [ [ 120, 155 ] ], "normalized": [] }, { "id": "53", "type": "virus", "text": [ "HIV-2" ], "offsets": [ [ 157, 162 ] ], "normalized": [] }, { "id": "54", "type": "virus", "text": [ "HIV-1" ], "offsets": [ [ 170, 175 ] ], "normalized": [] }, { "id": "55", "type": "other_name", "text": [ "AIDS" ], "offsets": [ [ 184, 188 ] ], "normalized": [] }, { "id": "56", "type": "other_name", "text": [ "AIDS" ], "offsets": [ [ 212, 216 ] ], "normalized": [] }, { "id": "57", "type": "virus", "text": [ "HIV-1" ], "offsets": [ [ 249, 254 ] ], "normalized": [] }, { "id": "58", "type": "virus", "text": [ "HIV-2" ], "offsets": [ [ 259, 264 ] ], "normalized": [] }, { "id": "59", "type": "DNA_N/A", "text": [ "nucleic acid sequence" ], "offsets": [ [ 300, 321 ] ], "normalized": [] }, { "id": "60", "type": "DNA_domain_or_region", "text": [ "enhancer/promoter region" ], "offsets": [ [ 446, 470 ] ], "normalized": [] }, { "id": "61", "type": "virus", "text": [ "HIV-2" ], "offsets": [ [ 474, 479 ] ], "normalized": [] }, { "id": "62", "type": "virus", "text": [ "HIV-1" ], "offsets": [ [ 521, 526 ] ], "normalized": [] }, { "id": "63", "type": "DNA_domain_or_region", "text": [ "HIV-1 enhancer" ], "offsets": [ [ 554, 568 ] ], "normalized": [] }, { "id": "64", "type": "virus", "text": [ "HIV-1" ], "offsets": [ [ 554, 559 ] ], "normalized": [] }, { "id": "65", "type": "other_name", "text": [ "T-cell stimulation" ], "offsets": [ [ 579, 597 ] ], "normalized": [] }, { "id": "66", "type": "protein_family_or_group", "text": [ "transcription factor" ], "offsets": [ [ 641, 661 ] ], "normalized": [] }, { "id": "67", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 662, 672 ] ], "normalized": [] }, { "id": "68", "type": "DNA_domain_or_region", "text": [ "kappa B sites" ], "offsets": [ [ 689, 702 ] ], "normalized": [] }, { "id": "69", "type": "DNA_domain_or_region", "text": [ "HIV-1 long terminal repeat" ], "offsets": [ [ 710, 736 ] ], "normalized": [] }, { "id": "70", "type": "virus", "text": [ "HIV-1" ], "offsets": [ [ 710, 715 ] ], "normalized": [] }, { "id": "71", "type": "DNA_domain_or_region", "text": [ "HIV-2 enhancer" ], "offsets": [ [ 756, 770 ] ], "normalized": [] }, { "id": "72", "type": "virus", "text": [ "HIV-2" ], "offsets": [ [ 756, 761 ] ], "normalized": [] }, { "id": "73", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 774, 783 ] ], "normalized": [] }, { "id": "74", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 788, 795 ] ], "normalized": [] }, { "id": "75", "type": "DNA_domain_or_region", "text": [ "cis-acting elements" ], "offsets": [ [ 817, 836 ] ], "normalized": [] }, { "id": "76", "type": "DNA_domain_or_region", "text": [ "kappa B site" ], "offsets": [ [ 689, 701 ] ], "normalized": [] }, { "id": "77", "type": "DNA_domain_or_region", "text": [ "purine-rich binding sites" ], "offsets": [ [ 865, 890 ] ], "normalized": [] }, { "id": "78", "type": "DNA_domain_or_region", "text": [ "PuB1" ], "offsets": [ [ 892, 896 ] ], "normalized": [] }, { "id": "79", "type": "DNA_domain_or_region", "text": [ "PuB2" ], "offsets": [ [ 901, 905 ] ], "normalized": [] }, { "id": "80", "type": "DNA_domain_or_region", "text": [ "pets site" ], "offsets": [ [ 913, 922 ] ], "normalized": [] }, { "id": "81", "type": "DNA_family_or_group", "text": [ "cis-acting element" ], "offsets": [ [ 955, 973 ] ], "normalized": [] }, { "id": "82", "type": "DNA_domain_or_region", "text": [ "HIV-2 enhancer" ], "offsets": [ [ 985, 999 ] ], "normalized": [] }, { "id": "83", "type": "virus", "text": [ "HIV-2" ], "offsets": [ [ 985, 990 ] ], "normalized": [] }, { "id": "84", "type": "DNA_domain_or_region", "text": [ "kappa B site" ], "offsets": [ [ 1029, 1041 ] ], "normalized": [] }, { "id": "85", "type": "DNA_domain_or_region", "text": [ "peri-kappa B" ], "offsets": [ [ 1054, 1066 ] ], "normalized": [] }, { "id": "86", "type": "virus", "text": [ "HIV-2" ], "offsets": [ [ 1109, 1114 ] ], "normalized": [] }, { "id": "87", "type": "virus", "text": [ "simian immunodeficiency virus" ], "offsets": [ [ 1139, 1168 ] ], "normalized": [] }, { "id": "88", "type": "other_name", "text": [ "transfection assays" ], "offsets": [ [ 1174, 1193 ] ], "normalized": [] }, { "id": "89", "type": "other_name", "text": [ "HIV-2 enhancer activation" ], "offsets": [ [ 1220, 1245 ] ], "normalized": [] }, { "id": "90", "type": "DNA_domain_or_region", "text": [ "HIV-2 enhancer" ], "offsets": [ [ 1220, 1234 ] ], "normalized": [] }, { "id": "91", "type": "virus", "text": [ "HIV-2" ], "offsets": [ [ 1220, 1225 ] ], "normalized": [] }, { "id": "92", "type": "cell_line", "text": [ "monocytic" ], "offsets": [ [ 1271, 1280 ] ], "normalized": [] }, { "id": "93", "type": "cell_line", "text": [ "T-cell lines" ], "offsets": [ [ 1289, 1301 ] ], "normalized": [] }, { "id": "94", "type": "DNA_domain_or_region", "text": [ "HIV-2 enhancer element" ], "offsets": [ [ 1339, 1361 ] ], "normalized": [] }, { "id": "95", "type": "virus", "text": [ "HIV-2" ], "offsets": [ [ 1339, 1344 ] ], "normalized": [] }, { "id": "96", "type": "DNA_domain_or_region", "text": [ "enhancer element" ], "offsets": [ [ 1345, 1361 ] ], "normalized": [] }, { "id": "97", "type": "virus", "text": [ "HIV-1" ], "offsets": [ [ 1468, 1473 ] ], "normalized": [] }, { "id": "98", "type": "protein_family_or_group", "text": [ "nuclear factor" ], "offsets": [ [ 1483, 1497 ] ], "normalized": [] }, { "id": "99", "type": "cell_type", "text": [ "peripheral blood monocytes" ], "offsets": [ [ 1511, 1537 ] ], "normalized": [] }, { "id": "100", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 1528, 1537 ] ], "normalized": [] }, { "id": "101", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 1542, 1549 ] ], "normalized": [] }, { "id": "102", "type": "DNA_domain_or_region", "text": [ "peri-kappa B site" ], "offsets": [ [ 1560, 1577 ] ], "normalized": [] }, { "id": "103", "type": "other_name", "text": [ "electrophoretic mobility shift assays" ], "offsets": [ [ 1579, 1616 ] ], "normalized": [] }, { "id": "104", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 1679, 1688 ] ], "normalized": [] }, { "id": "105", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 1696, 1703 ] ], "normalized": [] }, { "id": "106", "type": "DNA_domain_or_region", "text": [ "enhancer element" ], "offsets": [ [ 1741, 1757 ] ], "normalized": [] }, { "id": "107", "type": "other_name", "text": [ "differential modification" ], "offsets": [ [ 1768, 1793 ] ], "normalized": [] }, { "id": "108", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 1797, 1806 ] ], "normalized": [] }, { "id": "109", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 1811, 1818 ] ], "normalized": [] }, { "id": "110", "type": "DNA_domain_or_region", "text": [ "peri-kappa B site" ], "offsets": [ [ 1911, 1928 ] ], "normalized": [] }, { "id": "111", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 1940, 1949 ] ], "normalized": [] }, { "id": "112", "type": "other_organic_compound", "text": [ "phorbol esters" ], "offsets": [ [ 1968, 1982 ] ], "normalized": [] }, { "id": "113", "type": "other_name", "text": [ "monocyte-specific function" ], "offsets": [ [ 2039, 2065 ] ], "normalized": [] }, { "id": "114", "type": "protein_molecule", "text": [ "peri-kappa B factor" ], "offsets": [ [ 2073, 2092 ] ], "normalized": [] }, { "id": "115", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 2148, 2157 ] ], "normalized": [] }, { "id": "116", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 2162, 2169 ] ], "normalized": [] }, { "id": "117", "type": "other_name", "text": [ "HIV pathogenesis" ], "offsets": [ [ 2178, 2194 ] ], "normalized": [] } ]

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[ { "id": "119", "type": "title", "text": [ "E1A gene expression induces susceptibility to killing by NK cells following immortalization but not adenovirus infection of human cells." ], "offsets": [ [ 0, 136 ] ] }, { "id": "120", "type": "abstract", "text": [ "Adenovirus (Ad) infection and E1A transfection were used to model changes in susceptibility to NK cell killing caused by transient vs stable E1A expression in human cells. Only stably transfected target cells exhibited cytolytic susceptibility, despite expression of equivalent levels of E1A proteins in Ad-infected targets. The inability of E1A gene products to induce cytolytic susceptibility during infection was not explained by an inhibitory effect of viral infection on otherwise susceptible target cells or by viral gene effects on class I MHC antigen expression on target cells. This differential effect of E1A expression on the cytolytic phenotypes of infected and stably transfected human cells suggests that human NK cells provide an effective immunologic barrier against the in vivo survival and neoplastic progression of E1A-immortalized cells that may emerge from the reservoir of persistently infected cells in the human host." ], "offsets": [ [ 137, 1078 ] ] } ]

[ { "id": "121", "type": "other_name", "text": [ "E1A gene expression" ], "offsets": [ [ 0, 19 ] ], "normalized": [] }, { "id": "122", "type": "DNA_domain_or_region", "text": [ "E1A gene" ], "offsets": [ [ 0, 8 ] ], "normalized": [] }, { "id": "123", "type": "cell_type", "text": [ "NK cells" ], "offsets": [ [ 57, 65 ] ], "normalized": [] }, { "id": "124", "type": "other_name", "text": [ "adenovirus infection" ], "offsets": [ [ 100, 120 ] ], "normalized": [] }, { "id": "125", "type": "virus", "text": [ "adenovirus" ], "offsets": [ [ 100, 110 ] ], "normalized": [] }, { "id": "126", "type": "cell_type", "text": [ "human cells" ], "offsets": [ [ 124, 135 ] ], "normalized": [] }, { "id": "127", "type": "other_name", "text": [ "Adenovirus (Ad) infection" ], "offsets": [ [ 137, 162 ] ], "normalized": [] }, { "id": "128", "type": "virus", "text": [ "Adenovirus" ], "offsets": [ [ 137, 147 ] ], "normalized": [] }, { "id": "129", "type": "other_name", "text": [ "E1A transfection" ], "offsets": [ [ 167, 183 ] ], "normalized": [] }, { "id": "130", "type": "protein_molecule", "text": [ "E1A" ], "offsets": [ [ 167, 170 ] ], "normalized": [] }, { "id": "131", "type": "other_name", "text": [ "NK cell killing" ], "offsets": [ [ 232, 247 ] ], "normalized": [] }, { "id": "132", "type": "other_name", "text": [ "E1A expression" ], "offsets": [ [ 278, 292 ] ], "normalized": [] }, { "id": "133", "type": "protein_molecule", "text": [ "E1A" ], "offsets": [ [ 278, 281 ] ], "normalized": [] }, { "id": "134", "type": "cell_type", "text": [ "human cells" ], "offsets": [ [ 296, 307 ] ], "normalized": [] }, { "id": "135", "type": "cell_line", "text": [ "transfected target cells" ], "offsets": [ [ 321, 345 ] ], "normalized": [] }, { "id": "136", "type": "protein_family_or_group", "text": [ "E1A proteins" ], "offsets": [ [ 425, 437 ] ], "normalized": [] }, { "id": "137", "type": "cell_line", "text": [ "Ad-infected targets" ], "offsets": [ [ 441, 460 ] ], "normalized": [] }, { "id": "138", "type": "DNA_domain_or_region", "text": [ "E1A gene" ], "offsets": [ [ 479, 487 ] ], "normalized": [] }, { "id": "139", "type": "other_name", "text": [ "cytolytic susceptibility" ], "offsets": [ [ 507, 531 ] ], "normalized": [] }, { "id": "140", "type": "cell_type", "text": [ "target cells" ], "offsets": [ [ 635, 647 ] ], "normalized": [] }, { "id": "141", "type": "DNA_domain_or_region", "text": [ "viral gene" ], "offsets": [ [ 654, 664 ] ], "normalized": [] }, { "id": "142", "type": "other_name", "text": [ "class I MHC antigen expression" ], "offsets": [ [ 676, 706 ] ], "normalized": [] }, { "id": "143", "type": "protein_family_or_group", "text": [ "class I MHC antigen" ], "offsets": [ [ 676, 695 ] ], "normalized": [] }, { "id": "144", "type": "cell_type", "text": [ "target cells" ], "offsets": [ [ 710, 722 ] ], "normalized": [] }, { "id": "145", "type": "other_name", "text": [ "E1A expression" ], "offsets": [ [ 752, 766 ] ], "normalized": [] }, { "id": "146", "type": "protein_molecule", "text": [ "E1A" ], "offsets": [ [ 752, 755 ] ], "normalized": [] }, { "id": "147", "type": "cell_type", "text": [ "human cells" ], "offsets": [ [ 830, 841 ] ], "normalized": [] }, { "id": "148", "type": "cell_type", "text": [ "human NK cells" ], "offsets": [ [ 856, 870 ] ], "normalized": [] }, { "id": "149", "type": "cell_type", "text": [ "NK cells" ], "offsets": [ [ 862, 870 ] ], "normalized": [] }, { "id": "150", "type": "other_name", "text": [ "neoplastic progression" ], "offsets": [ [ 945, 967 ] ], "normalized": [] }, { "id": "151", "type": "cell_line", "text": [ "E1A-immortalized cells" ], "offsets": [ [ 971, 993 ] ], "normalized": [] }, { "id": "152", "type": "cell_type", "text": [ "persistently infected cells" ], "offsets": [ [ 1032, 1059 ] ], "normalized": [] }, { "id": "153", "type": "multi_cell", "text": [ "human host" ], "offsets": [ [ 1067, 1077 ] ], "normalized": [] } ]

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[ { "id": "155", "type": "title", "text": [ "Distinct signaling properties identify functionally different CD4 epitopes." ], "offsets": [ [ 0, 75 ] ] }, { "id": "156", "type": "abstract", "text": [ "The CD4 coreceptor interacts with non-polymorphic regions of major histocompatibility complex class II molecules on antigen-presenting cells and contributes to T cell activation. We have investigated the effect of CD4 triggering on T cell activating signals in a lymphoma model using monoclonal antibodies (mAb) which recognize different CD4 epitopes. We demonstrate that CD4 triggering delivers signals capable of activating the NF-AT transcription factor which is required for interleukin-2 gene expression. Whereas different anti-CD4 mAb or HIV-1 gp120 could all trigger activation of the protein tyrosine kinases p56lck and p59fyn and phosphorylation of the Shc adaptor protein, which mediates signals to Ras, they differed significantly in their ability to activate NF-AT. Lack of full activation of NF-AT could be correlated to a dramatically reduced capacity to induce calcium flux and could be complemented with a calcium ionophore. The results identify functionally distinct epitopes on the CD4 coreceptor involved in activation of the Ras/protein kinase C and calcium pathways." ], "offsets": [ [ 76, 1163 ] ] } ]

[ { "id": "157", "type": "protein_family_or_group", "text": [ "CD4 epitopes" ], "offsets": [ [ 62, 74 ] ], "normalized": [] }, { "id": "158", "type": "protein_molecule", "text": [ "CD4 coreceptor" ], "offsets": [ [ 80, 94 ] ], "normalized": [] }, { "id": "159", "type": "protein_domain_or_region", "text": [ "non-polymorphic regions" ], "offsets": [ [ 110, 133 ] ], "normalized": [] }, { "id": "160", "type": "protein_family_or_group", "text": [ "major histocompatibility complex class II molecules" ], "offsets": [ [ 137, 188 ] ], "normalized": [] }, { "id": "161", "type": "cell_type", "text": [ "antigen-presenting cells" ], "offsets": [ [ 192, 216 ] ], "normalized": [] }, { "id": "162", "type": "other_name", "text": [ "T cell activation" ], "offsets": [ [ 236, 253 ] ], "normalized": [] }, { "id": "163", "type": "other_name", "text": [ "CD4 triggering" ], "offsets": [ [ 290, 304 ] ], "normalized": [] }, { "id": "164", "type": "protein_molecule", "text": [ "CD4" ], "offsets": [ [ 290, 293 ] ], "normalized": [] }, { "id": "165", "type": "other_name", "text": [ "T cell activating signals" ], "offsets": [ [ 308, 333 ] ], "normalized": [] }, { "id": "166", "type": "other_name", "text": [ "lymphoma model" ], "offsets": [ [ 339, 353 ] ], "normalized": [] }, { "id": "167", "type": "protein_family_or_group", "text": [ "monoclonal antibodies" ], "offsets": [ [ 360, 381 ] ], "normalized": [] }, { "id": "168", "type": "protein_domain_or_region", "text": [ "mAb" ], "offsets": [ [ 383, 386 ] ], "normalized": [] }, { "id": "169", "type": "protein_family_or_group", "text": [ "CD4 epitopes" ], "offsets": [ [ 414, 426 ] ], "normalized": [] }, { "id": "170", "type": "other_name", "text": [ "CD4 triggering" ], "offsets": [ [ 448, 462 ] ], "normalized": [] }, { "id": "171", "type": "protein_molecule", "text": [ "CD4" ], "offsets": [ [ 448, 451 ] ], "normalized": [] }, { "id": "172", "type": "protein_molecule", "text": [ "NF-AT transcription factor" ], "offsets": [ [ 506, 532 ] ], "normalized": [] }, { "id": "173", "type": "other_name", "text": [ "interleukin-2 gene expression" ], "offsets": [ [ 555, 584 ] ], "normalized": [] }, { "id": "174", "type": "protein_molecule", "text": [ "interleukin-2" ], "offsets": [ [ 555, 568 ] ], "normalized": [] }, { "id": "175", "type": "protein_family_or_group", "text": [ "anti-CD4 mAb" ], "offsets": [ [ 604, 616 ] ], "normalized": [] }, { "id": "176", "type": "protein_molecule", "text": [ "HIV-1 gp120" ], "offsets": [ [ 620, 631 ] ], "normalized": [] }, { "id": "177", "type": "virus", "text": [ "HIV-1" ], "offsets": [ [ 620, 625 ] ], "normalized": [] }, { "id": "178", "type": "protein_family_or_group", "text": [ "protein tyrosine kinases" ], "offsets": [ [ 668, 692 ] ], "normalized": [] }, { "id": "179", "type": "protein_molecule", "text": [ "p56lck" ], "offsets": [ [ 693, 699 ] ], "normalized": [] }, { "id": "180", "type": "protein_molecule", "text": [ "p59fyn" ], "offsets": [ [ 704, 710 ] ], "normalized": [] }, { "id": "181", "type": "protein_molecule", "text": [ "Shc adaptor protein" ], "offsets": [ [ 738, 757 ] ], "normalized": [] }, { "id": "182", "type": "protein_family_or_group", "text": [ "Ras" ], "offsets": [ [ 785, 788 ] ], "normalized": [] }, { "id": "183", "type": "protein_molecule", "text": [ "NF-AT" ], "offsets": [ [ 847, 852 ] ], "normalized": [] }, { "id": "184", "type": "protein_molecule", "text": [ "NF-AT" ], "offsets": [ [ 881, 886 ] ], "normalized": [] }, { "id": "185", "type": "other_name", "text": [ "calcium flux" ], "offsets": [ [ 952, 964 ] ], "normalized": [] }, { "id": "186", "type": "atom", "text": [ "calcium" ], "offsets": [ [ 952, 959 ] ], "normalized": [] }, { "id": "187", "type": "other_organic_compound", "text": [ "calcium ionophore" ], "offsets": [ [ 998, 1015 ] ], "normalized": [] }, { "id": "188", "type": "protein_family_or_group", "text": [ "epitopes" ], "offsets": [ [ 1060, 1068 ] ], "normalized": [] }, { "id": "189", "type": "protein_molecule", "text": [ "CD4 coreceptor" ], "offsets": [ [ 1076, 1090 ] ], "normalized": [] }, { "id": "190", "type": "other_name", "text": [ "Ras/protein kinase C and calcium pathways" ], "offsets": [ [ 1121, 1162 ] ], "normalized": [] }, { "id": "191", "type": "protein_molecule", "text": [ "Ras/protein kinase C" ], "offsets": [ [ 1121, 1141 ] ], "normalized": [] }, { "id": "192", "type": "other_name", "text": [ "Ras/protein kinase C" ], "offsets": [ [ 1121, 1141 ] ], "normalized": [] }, { "id": "193", "type": "protein_molecule", "text": [ "Ras" ], "offsets": [ [ 1121, 1124 ] ], "normalized": [] }, { "id": "194", "type": "protein_molecule", "text": [ "/protein kinase C" ], "offsets": [ [ 1124, 1141 ] ], "normalized": [] }, { "id": "195", "type": "other_name", "text": [ "calcium pathways" ], "offsets": [ [ 1146, 1162 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "197", "type": "title", "text": [ "Ligand-dependent repression of the erythroid transcription factor GATA-1 by the estrogen receptor." ], "offsets": [ [ 0, 98 ] ] }, { "id": "198", "type": "abstract", "text": [ "High-dose estrogen administration induces anemia in mammals. In chickens, estrogens stimulate outgrowth of bone marrow-derived erythroid progenitor cells and delay their maturation. This delay is associated with down-regulation of many erythroid cell-specific genes, including alpha- and beta-globin, band 3, band 4.1, and the erythroid cell-specific histone H5. We show here that estrogens also reduce the number of erythroid progenitor cells in primary human bone marrow cultures. To address potential mechanisms by which estrogens suppress erythropoiesis, we have examined their effects on GATA-1, an erythroid transcription factor that participates in the regulation of the majority of erythroid cell-specific genes and is necessary for full maturation of erythrocytes. We demonstrate that the transcriptional activity of GATA-1 is strongly repressed by the estrogen receptor (ER) in a ligand-dependent manner and that this repression is reversible in the presence of 4-hydroxytamoxifen. ER-mediated repression of GATA-1 activity occurs on an artificial promoter containing a single GATA-binding site, as well as in the context of an intact promoter which is normally regulated by GATA-1. GATA-1 and ER bind to each other in vitro in the absence of DNA. In coimmunoprecipitation experiments using transfected COS cells, GATA-1 and ER associate in a ligand-dependent manner. Mapping experiments indicate that GATA-1 and the ER form at least two contacts, which involve the finger region and the N-terminal activation domain of GATA-1. We speculate that estrogens exert effects on erythropoiesis by modulating GATA-1 activity through protein-protein interaction with the ER. (ABSTRACT TRUNCATED AT 250 WORDS)" ], "offsets": [ [ 99, 1809 ] ] } ]

[ { "id": "199", "type": "other_name", "text": [ "Ligand-dependent repression" ], "offsets": [ [ 0, 27 ] ], "normalized": [] }, { "id": "200", "type": "protein_family_or_group", "text": [ "erythroid transcription factor" ], "offsets": [ [ 35, 65 ] ], "normalized": [] }, { "id": "201", "type": "protein_molecule", "text": [ "GATA-1" ], "offsets": [ [ 66, 72 ] ], "normalized": [] }, { "id": "202", "type": "protein_family_or_group", "text": [ "estrogen receptor" ], "offsets": [ [ 80, 97 ] ], "normalized": [] }, { "id": "203", "type": "other_name", "text": [ "High-dose estrogen administration" ], "offsets": [ [ 99, 132 ] ], "normalized": [] }, { "id": "204", "type": "other_name", "text": [ "anemia" ], "offsets": [ [ 141, 147 ] ], "normalized": [] }, { "id": "205", "type": "multi_cell", "text": [ "mammals" ], "offsets": [ [ 151, 158 ] ], "normalized": [] }, { "id": "206", "type": "cell_type", "text": [ "bone marrow-derived erythroid progenitor cells" ], "offsets": [ [ 206, 252 ] ], "normalized": [] }, { "id": "207", "type": "other_name", "text": [ "maturation" ], "offsets": [ [ 269, 279 ] ], "normalized": [] }, { "id": "208", "type": "other_name", "text": [ "down-regulation" ], "offsets": [ [ 311, 326 ] ], "normalized": [] }, { "id": "209", "type": "DNA_family_or_group", "text": [ "erythroid cell-specific genes" ], "offsets": [ [ 335, 364 ] ], "normalized": [] }, { "id": "210", "type": "(AND DNA_domain_or_region DNA_domain_or_region)", "text": [ "alpha- and beta-globin" ], "offsets": [ [ 376, 398 ] ], "normalized": [] }, { "id": "211", "type": "", "text": [ "alpha-" ], "offsets": [ [ 376, 382 ] ], "normalized": [] }, { "id": "212", "type": "", "text": [ "beta-" ], "offsets": [ [ 387, 392 ] ], "normalized": [] }, { "id": "213", "type": "", "text": [ "globin" ], "offsets": [ [ 392, 398 ] ], "normalized": [] }, { "id": "214", "type": "DNA_N/A", "text": [ "band 3" ], "offsets": [ [ 400, 406 ] ], "normalized": [] }, { "id": "215", "type": "DNA_N/A", "text": [ "band 4.1" ], "offsets": [ [ 408, 416 ] ], "normalized": [] }, { "id": "216", "type": "protein_molecule", "text": [ "erythroid cell-specific histone" ], "offsets": [ [ 426, 457 ] ], "normalized": [] }, { "id": "217", "type": "protein_molecule", "text": [ "H5" ], "offsets": [ [ 458, 460 ] ], "normalized": [] }, { "id": "218", "type": "cell_type", "text": [ "erythroid progenitor cells" ], "offsets": [ [ 516, 542 ] ], "normalized": [] }, { "id": "219", "type": "cell_line", "text": [ "primary human bone marrow cultures" ], "offsets": [ [ 546, 580 ] ], "normalized": [] }, { "id": "220", "type": "lipid", "text": [ "estrogens" ], "offsets": [ [ 623, 632 ] ], "normalized": [] }, { "id": "221", "type": "other_name", "text": [ "erythropoiesis" ], "offsets": [ [ 642, 656 ] ], "normalized": [] }, { "id": "222", "type": "protein_molecule", "text": [ "GATA-1" ], "offsets": [ [ 692, 698 ] ], "normalized": [] }, { "id": "223", "type": "protein_family_or_group", "text": [ "erythroid transcription factor" ], "offsets": [ [ 703, 733 ] ], "normalized": [] }, { "id": "224", "type": "DNA_domain_or_region", "text": [ "erythroid cell-specific genes" ], "offsets": [ [ 789, 818 ] ], "normalized": [] }, { "id": "225", "type": "cell_type", "text": [ "erythrocytes" ], "offsets": [ [ 859, 871 ] ], "normalized": [] }, { "id": "226", "type": "other_name", "text": [ "transcriptional activity" ], "offsets": [ [ 897, 921 ] ], "normalized": [] }, { "id": "227", "type": "protein_molecule", "text": [ "GATA-1" ], "offsets": [ [ 925, 931 ] ], "normalized": [] }, { "id": "228", "type": "protein_family_or_group", "text": [ "estrogen receptor" ], "offsets": [ [ 961, 978 ] ], "normalized": [] }, { "id": "229", "type": "protein_family_or_group", "text": [ "ER" ], "offsets": [ [ 980, 982 ] ], "normalized": [] }, { "id": "230", "type": "other_name", "text": [ "repression" ], "offsets": [ [ 1027, 1037 ] ], "normalized": [] }, { "id": "231", "type": "other_organic_compound", "text": [ "4-hydroxytamoxifen" ], "offsets": [ [ 1071, 1089 ] ], "normalized": [] }, { "id": "232", "type": "other_name", "text": [ "ER-mediated repression" ], "offsets": [ [ 1091, 1113 ] ], "normalized": [] }, { "id": "233", "type": "protein_family_or_group", "text": [ "ER" ], "offsets": [ [ 1091, 1093 ] ], "normalized": [] }, { "id": "234", "type": "other_name", "text": [ "GATA-1 activity" ], "offsets": [ [ 1117, 1132 ] ], "normalized": [] }, { "id": "235", "type": "protein_molecule", "text": [ "GATA-1" ], "offsets": [ [ 1117, 1123 ] ], "normalized": [] }, { "id": "236", "type": "DNA_molecule", "text": [ "artificial promoter" ], "offsets": [ [ 1146, 1165 ] ], "normalized": [] }, { "id": "237", "type": "DNA_domain_or_region", "text": [ "GATA-binding site" ], "offsets": [ [ 1186, 1203 ] ], "normalized": [] }, { "id": "238", "type": "DNA_domain_or_region", "text": [ "intact promoter" ], "offsets": [ [ 1237, 1252 ] ], "normalized": [] }, { "id": "239", "type": "protein_molecule", "text": [ "GATA-1" ], "offsets": [ [ 1284, 1290 ] ], "normalized": [] }, { "id": "240", "type": "protein_molecule", "text": [ "GATA-1" ], "offsets": [ [ 1292, 1298 ] ], "normalized": [] }, { "id": "241", "type": "protein_family_or_group", "text": [ "ER" ], "offsets": [ [ 1303, 1305 ] ], "normalized": [] }, { "id": "242", "type": "other_name", "text": [ "coimmunoprecipitation experiments" ], "offsets": [ [ 1360, 1393 ] ], "normalized": [] }, { "id": "243", "type": "cell_line", "text": [ "COS cells" ], "offsets": [ [ 1412, 1421 ] ], "normalized": [] }, { "id": "244", "type": "protein_molecule", "text": [ "GATA-1" ], "offsets": [ [ 1423, 1429 ] ], "normalized": [] }, { "id": "245", "type": "protein_family_or_group", "text": [ "ER" ], "offsets": [ [ 1434, 1436 ] ], "normalized": [] }, { "id": "246", "type": "other_name", "text": [ "ligand-dependent manner" ], "offsets": [ [ 1452, 1475 ] ], "normalized": [] }, { "id": "247", "type": "protein_molecule", "text": [ "GATA-1" ], "offsets": [ [ 1511, 1517 ] ], "normalized": [] }, { "id": "248", "type": "protein_family_or_group", "text": [ "ER" ], "offsets": [ [ 1526, 1528 ] ], "normalized": [] }, { "id": "249", "type": "protein_domain_or_region", "text": [ "N-terminal activation domain" ], "offsets": [ [ 1597, 1625 ] ], "normalized": [] }, { "id": "250", "type": "protein_molecule", "text": [ "GATA-1" ], "offsets": [ [ 1629, 1635 ] ], "normalized": [] }, { "id": "251", "type": "lipid", "text": [ "estrogens" ], "offsets": [ [ 1655, 1664 ] ], "normalized": [] }, { "id": "252", "type": "other_name", "text": [ "erythropoiesis" ], "offsets": [ [ 1682, 1696 ] ], "normalized": [] }, { "id": "253", "type": "other_name", "text": [ "GATA-1 activity" ], "offsets": [ [ 1711, 1726 ] ], "normalized": [] }, { "id": "254", "type": "protein_molecule", "text": [ "GATA-1" ], "offsets": [ [ 1711, 1717 ] ], "normalized": [] }, { "id": "255", "type": "other_name", "text": [ "protein-protein interaction" ], "offsets": [ [ 1735, 1762 ] ], "normalized": [] }, { "id": "256", "type": "protein_family_or_group", "text": [ "ER" ], "offsets": [ [ 1772, 1774 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "258", "type": "title", "text": [ "Mouse interleukin-2 receptor alpha gene expression. Interleukin-1 and interleukin-2 control transcription via distinct cis-acting elements." ], "offsets": [ [ 0, 139 ] ] }, { "id": "259", "type": "abstract", "text": [ "We have shown that interleukin-1 (IL-1) and IL-2 control IL-2 receptor alpha (IL-2R alpha) gene transcription in CD4-CD8- murine T lymphocyte precursors. Here we map the cis-acting elements that mediate interleukin responsiveness of the mouse IL-2R alpha gene using a thymic lymphoma-derived hybridoma (PC60). The transcriptional response of the IL-2R alpha gene to stimulation by IL-1 + IL-2 is biphasic. IL-1 induces a rapid, protein synthesis-independent appearance of IL-2R alpha mRNA that is blocked by inhibitors of NF-kappa B activation. It also primes cells to become IL-2 responsive and thereby prepares the second phase, in which IL-2 induces a 100-fold further increase in IL-2R alpha transcripts. Transient transfection experiments show that several elements in the promoter-proximal region of the IL-2R alpha gene contribute to IL-1 responsiveness, most importantly an NF-kappa B site conserved in the human and mouse gene. IL-2 responsiveness, on the other hand, depends on a 78-nucleotide segment 1.3 kilobases upstream of the major transcription start site. This segment functions as an IL-2-inducible enhancer and lies within a region that becomes DNase I hypersensitive in normal T cells in which IL-2R alpha expression has been induced. IL-2 responsiveness requires three distinct elements within the enhancer. Two of these are potential binding sites for STAT proteins." ], "offsets": [ [ 140, 1529 ] ] } ]

[ { "id": "260", "type": "other_name", "text": [ "Mouse interleukin-2 receptor alpha gene expression" ], "offsets": [ [ 0, 50 ] ], "normalized": [] }, { "id": "261", "type": "DNA_domain_or_region", "text": [ "Mouse interleukin-2 receptor alpha gene" ], "offsets": [ [ 0, 39 ] ], "normalized": [] }, { "id": "262", "type": "protein_molecule", "text": [ "interleukin-2" ], "offsets": [ [ 6, 19 ] ], "normalized": [] }, { "id": "263", "type": "protein_molecule", "text": [ "Interleukin-1" ], "offsets": [ [ 52, 65 ] ], "normalized": [] }, { "id": "264", "type": "protein_molecule", "text": [ "interleukin-2" ], "offsets": [ [ 70, 83 ] ], "normalized": [] }, { "id": "265", "type": "DNA_family_or_group", "text": [ "cis-acting elements" ], "offsets": [ [ 119, 138 ] ], "normalized": [] }, { "id": "266", "type": "protein_molecule", "text": [ "interleukin-1" ], "offsets": [ [ 159, 172 ] ], "normalized": [] }, { "id": "267", "type": "protein_molecule", "text": [ "IL-1" ], "offsets": [ [ 174, 178 ] ], "normalized": [] }, { "id": "268", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 184, 188 ] ], "normalized": [] }, { "id": "269", "type": "other_name", "text": [ "IL-2 receptor alpha (IL-2R alpha) gene transcription" ], "offsets": [ [ 197, 249 ] ], "normalized": [] }, { "id": "270", "type": "DNA_domain_or_region", "text": [ "IL-2 receptor alpha (IL-2R alpha) gene" ], "offsets": [ [ 197, 235 ] ], "normalized": [] }, { "id": "271", "type": "protein_molecule", "text": [ "IL-2 receptor alpha" ], "offsets": [ [ 197, 216 ] ], "normalized": [] }, { "id": "272", "type": "protein_molecule", "text": [ "IL-2R alpha" ], "offsets": [ [ 218, 229 ] ], "normalized": [] }, { "id": "273", "type": "cell_line", "text": [ "CD4-CD8- murine T lymphocyte precursors" ], "offsets": [ [ 253, 292 ] ], "normalized": [] }, { "id": "274", "type": "DNA_family_or_group", "text": [ "cis-acting elements" ], "offsets": [ [ 310, 329 ] ], "normalized": [] }, { "id": "275", "type": "DNA_domain_or_region", "text": [ "mouse IL-2R alpha gene" ], "offsets": [ [ 377, 399 ] ], "normalized": [] }, { "id": "276", "type": "protein_molecule", "text": [ "mouse IL-2R alpha" ], "offsets": [ [ 377, 394 ] ], "normalized": [] }, { "id": "277", "type": "cell_line", "text": [ "thymic lymphoma-derived hybridoma" ], "offsets": [ [ 408, 441 ] ], "normalized": [] }, { "id": "278", "type": "cell_line", "text": [ "PC60" ], "offsets": [ [ 443, 447 ] ], "normalized": [] }, { "id": "279", "type": "DNA_domain_or_region", "text": [ "IL-2R alpha gene" ], "offsets": [ [ 486, 502 ] ], "normalized": [] }, { "id": "280", "type": "protein_molecule", "text": [ "IL-1" ], "offsets": [ [ 521, 525 ] ], "normalized": [] }, { "id": "281", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 486, 490 ] ], "normalized": [] }, { "id": "282", "type": "protein_molecule", "text": [ "IL-1" ], "offsets": [ [ 546, 550 ] ], "normalized": [] }, { "id": "283", "type": "other_name", "text": [ "protein synthesis-independent appearance" ], "offsets": [ [ 568, 608 ] ], "normalized": [] }, { "id": "284", "type": "RNA_molecule", "text": [ "IL-2R alpha mRNA" ], "offsets": [ [ 612, 628 ] ], "normalized": [] }, { "id": "285", "type": "protein_molecule", "text": [ "IL-2R alpha" ], "offsets": [ [ 612, 623 ] ], "normalized": [] }, { "id": "286", "type": "other_name", "text": [ "NF-kappa B activation" ], "offsets": [ [ 662, 683 ] ], "normalized": [] }, { "id": "287", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 662, 672 ] ], "normalized": [] }, { "id": "288", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 716, 720 ] ], "normalized": [] }, { "id": "289", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 780, 784 ] ], "normalized": [] }, { "id": "290", "type": "RNA_family_or_group", "text": [ "IL-2R alpha transcripts" ], "offsets": [ [ 824, 847 ] ], "normalized": [] }, { "id": "291", "type": "protein_molecule", "text": [ "IL-2R alpha" ], "offsets": [ [ 824, 835 ] ], "normalized": [] }, { "id": "292", "type": "other_name", "text": [ "Transient transfection experiments" ], "offsets": [ [ 849, 883 ] ], "normalized": [] }, { "id": "293", "type": "DNA_domain_or_region", "text": [ "promoter-proximal region" ], "offsets": [ [ 918, 942 ] ], "normalized": [] }, { "id": "294", "type": "DNA_domain_or_region", "text": [ "IL-2R alpha gene" ], "offsets": [ [ 950, 966 ] ], "normalized": [] }, { "id": "295", "type": "protein_molecule", "text": [ "IL-2R alpha" ], "offsets": [ [ 950, 961 ] ], "normalized": [] }, { "id": "296", "type": "protein_molecule", "text": [ "IL-1" ], "offsets": [ [ 981, 985 ] ], "normalized": [] }, { "id": "297", "type": "DNA_domain_or_region", "text": [ "NF-kappa B site" ], "offsets": [ [ 1022, 1037 ] ], "normalized": [] }, { "id": "298", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 1022, 1032 ] ], "normalized": [] }, { "id": "299", "type": "(AND DNA_family_or_group DNA_family_or_group)", "text": [ "human and mouse gene" ], "offsets": [ [ 1055, 1075 ] ], "normalized": [] }, { "id": "300", "type": "", "text": [ "human" ], "offsets": [ [ 1055, 1060 ] ], "normalized": [] }, { "id": "301", "type": "", "text": [ "mouse" ], "offsets": [ [ 1065, 1070 ] ], "normalized": [] }, { "id": "302", "type": "", "text": [ "gene" ], "offsets": [ [ 962, 966 ] ], "normalized": [] }, { "id": "303", "type": "other_name", "text": [ "IL-2 responsiveness" ], "offsets": [ [ 1077, 1096 ] ], "normalized": [] }, { "id": "304", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 1077, 1081 ] ], "normalized": [] }, { "id": "305", "type": "DNA_domain_or_region", "text": [ "78-nucleotide segment" ], "offsets": [ [ 1130, 1151 ] ], "normalized": [] }, { "id": "306", "type": "DNA_domain_or_region", "text": [ "major transcription start site" ], "offsets": [ [ 1182, 1212 ] ], "normalized": [] }, { "id": "307", "type": "DNA_domain_or_region", "text": [ "IL-2-inducible enhancer" ], "offsets": [ [ 1243, 1266 ] ], "normalized": [] }, { "id": "308", "type": "other_name", "text": [ "DNase I hypersensitive" ], "offsets": [ [ 1305, 1327 ] ], "normalized": [] }, { "id": "309", "type": "protein_molecule", "text": [ "DNase I" ], "offsets": [ [ 1305, 1312 ] ], "normalized": [] }, { "id": "310", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 1338, 1345 ] ], "normalized": [] }, { "id": "311", "type": "other_name", "text": [ "IL-2R alpha expression" ], "offsets": [ [ 1355, 1377 ] ], "normalized": [] }, { "id": "312", "type": "protein_molecule", "text": [ "IL-2R alpha" ], "offsets": [ [ 1355, 1366 ] ], "normalized": [] }, { "id": "313", "type": "other_name", "text": [ "IL-2 responsiveness" ], "offsets": [ [ 1396, 1415 ] ], "normalized": [] }, { "id": "314", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 1396, 1400 ] ], "normalized": [] }, { "id": "315", "type": "DNA_domain_or_region", "text": [ "elements" ], "offsets": [ [ 1440, 1448 ] ], "normalized": [] }, { "id": "316", "type": "DNA_domain_or_region", "text": [ "enhancer" ], "offsets": [ [ 1460, 1468 ] ], "normalized": [] }, { "id": "317", "type": "protein_family_or_group", "text": [ "STAT proteins" ], "offsets": [ [ 1515, 1528 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "319", "type": "title", "text": [ "Hematopoietic lineage commitment: role of transcription factors." ], "offsets": [ [ 0, 64 ] ] }, { "id": "320", "type": "abstract", "text": [ "This review focuses on the roles of transcription factors in hematopoietic lineage commitment. A brief introduction to lineage commitment and asymmetric cell division is followed by a discussion of several methods used to identify transcription factors important in specifying hematopoietic cell types. Next is presented a discussion of the use of embryonic stem cells in the analysis of hematopoietic gene expression and the use of targeted gene disruption to analyze the role of transcription factors in hematopoiesis. Finally, the status of our current knowledge concerning the roles of transcription factors in the commitment to erythroid, myeloid and lymphoid cell types is summarized." ], "offsets": [ [ 65, 755 ] ] } ]

[ { "id": "321", "type": "other_name", "text": [ "Hematopoietic lineage commitment" ], "offsets": [ [ 0, 32 ] ], "normalized": [] }, { "id": "322", "type": "cell_type", "text": [ "Hematopoietic lineage" ], "offsets": [ [ 0, 21 ] ], "normalized": [] }, { "id": "323", "type": "protein_family_or_group", "text": [ "transcription factors" ], "offsets": [ [ 42, 63 ] ], "normalized": [] }, { "id": "324", "type": "protein_family_or_group", "text": [ "transcription factors" ], "offsets": [ [ 101, 122 ] ], "normalized": [] }, { "id": "325", "type": "other_name", "text": [ "hematopoietic lineage commitment" ], "offsets": [ [ 126, 158 ] ], "normalized": [] }, { "id": "326", "type": "other_name", "text": [ "lineage commitment" ], "offsets": [ [ 184, 202 ] ], "normalized": [] }, { "id": "327", "type": "other_name", "text": [ "asymmetric cell division" ], "offsets": [ [ 207, 231 ] ], "normalized": [] }, { "id": "328", "type": "protein_family_or_group", "text": [ "transcription factors" ], "offsets": [ [ 296, 317 ] ], "normalized": [] }, { "id": "329", "type": "cell_type", "text": [ "hematopoietic cell types" ], "offsets": [ [ 342, 366 ] ], "normalized": [] }, { "id": "330", "type": "cell_type", "text": [ "embryonic stem cells" ], "offsets": [ [ 413, 433 ] ], "normalized": [] }, { "id": "331", "type": "other_name", "text": [ "hematopoietic gene expression" ], "offsets": [ [ 453, 482 ] ], "normalized": [] }, { "id": "332", "type": "DNA_domain_or_region", "text": [ "hematopoietic gene" ], "offsets": [ [ 453, 471 ] ], "normalized": [] }, { "id": "333", "type": "other_name", "text": [ "targeted gene disruption" ], "offsets": [ [ 498, 522 ] ], "normalized": [] }, { "id": "334", "type": "protein_family_or_group", "text": [ "transcription factors" ], "offsets": [ [ 546, 567 ] ], "normalized": [] }, { "id": "335", "type": "other_name", "text": [ "hematopoiesis" ], "offsets": [ [ 571, 584 ] ], "normalized": [] }, { "id": "336", "type": "protein_family_or_group", "text": [ "transcription factors" ], "offsets": [ [ 655, 676 ] ], "normalized": [] }, { "id": "337", "type": "(AND cell_type cell_type cell_type)", "text": [ "erythroid, myeloid and lymphoid cell types" ], "offsets": [ [ 698, 740 ] ], "normalized": [] }, { "id": "338", "type": "", "text": [ "erythroid" ], "offsets": [ [ 698, 707 ] ], "normalized": [] }, { "id": "339", "type": "", "text": [ "myeloid" ], "offsets": [ [ 709, 716 ] ], "normalized": [] }, { "id": "340", "type": "", "text": [ "lymphoid" ], "offsets": [ [ 721, 729 ] ], "normalized": [] }, { "id": "341", "type": "", "text": [ "cell types" ], "offsets": [ [ 730, 740 ] ], "normalized": [] } ]

[]

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[ { "id": "343", "type": "title", "text": [ "Epstein-Barr virus replicative gene transcription during de novo infection of human thymocytes: simultaneous early expression of BZLF-1 and its repressor RAZ." ], "offsets": [ [ 0, 158 ] ] }, { "id": "344", "type": "abstract", "text": [ "Epstein-Barr virus (EBV) is known to infect B cells and epithelial cells. We and others have shown that EBV can also infect a subset of thymocytes. Infection of thymocytes was accompanied by the appearance of linear EBV genome within 8 hr of infection. Circularization of the EBV genome was not detected. This is in contrast to the infection in B cells where the genome can circularize within 24 hr of infection. The appearance of the BamHI ZLF-1 gene product, ZEBRA, by RT-PCR, was observed within 8 hr of infection. The appearance of a novel fusion transcript (RAZ), which comprised regions of the BZLF-1 locus and the adjacent BRLF-1 locus, was detected by RT-PCR. ZEBRA protein was also identified in infected thymocytes by immunoprecipitation. In addition, we demonstrated that the EBNA-1 gene in infected thymocytes was transcribed from the Fp promoter, rather than from the Cp/Wp promoter which is used in latently infected B cells. Transcripts encoding gp350/220, the major coat protein of EBV, were identified, but we did not find any evidence of transcription from the LMP-2A or EBER-1 loci in infected thymocytes. These observations suggest that de novo EBV infection of thymocytes differs from infection of B cells. The main difference is that with thymocytes, no evidence could be found that the virus ever circularizes. Rather, EBV remains in a linear configuration from which replicative genes are transcribed." ], "offsets": [ [ 159, 1584 ] ] } ]

[ { "id": "345", "type": "other_name", "text": [ "Epstein-Barr virus replicative gene transcription" ], "offsets": [ [ 0, 49 ] ], "normalized": [] }, { "id": "346", "type": "virus", "text": [ "Epstein-Barr virus" ], "offsets": [ [ 0, 18 ] ], "normalized": [] }, { "id": "347", "type": "other_name", "text": [ "de novo infection" ], "offsets": [ [ 57, 74 ] ], "normalized": [] }, { "id": "348", "type": "cell_type", "text": [ "human thymocytes" ], "offsets": [ [ 78, 94 ] ], "normalized": [] }, { "id": "349", "type": "other_name", "text": [ "simultaneous early expression" ], "offsets": [ [ 96, 125 ] ], "normalized": [] }, { "id": "350", "type": "protein_molecule", "text": [ "BZLF-1" ], "offsets": [ [ 129, 135 ] ], "normalized": [] }, { "id": "351", "type": "protein_molecule", "text": [ "RAZ" ], "offsets": [ [ 154, 157 ] ], "normalized": [] }, { "id": "352", "type": "virus", "text": [ "Epstein-Barr virus" ], "offsets": [ [ 159, 177 ] ], "normalized": [] }, { "id": "353", "type": "virus", "text": [ "EBV" ], "offsets": [ [ 179, 182 ] ], "normalized": [] }, { "id": "354", "type": "cell_type", "text": [ "B cells" ], "offsets": [ [ 203, 210 ] ], "normalized": [] }, { "id": "355", "type": "cell_type", "text": [ "epithelial cells" ], "offsets": [ [ 215, 231 ] ], "normalized": [] }, { "id": "356", "type": "virus", "text": [ "EBV" ], "offsets": [ [ 263, 266 ] ], "normalized": [] }, { "id": "357", "type": "cell_type", "text": [ "thymocytes" ], "offsets": [ [ 295, 305 ] ], "normalized": [] }, { "id": "358", "type": "cell_type", "text": [ "thymocytes" ], "offsets": [ [ 320, 330 ] ], "normalized": [] }, { "id": "359", "type": "DNA_family_or_group", "text": [ "linear EBV genome" ], "offsets": [ [ 368, 385 ] ], "normalized": [] }, { "id": "360", "type": "virus", "text": [ "EBV" ], "offsets": [ [ 375, 378 ] ], "normalized": [] }, { "id": "361", "type": "DNA_family_or_group", "text": [ "EBV genome" ], "offsets": [ [ 435, 445 ] ], "normalized": [] }, { "id": "362", "type": "virus", "text": [ "EBV" ], "offsets": [ [ 435, 438 ] ], "normalized": [] }, { "id": "363", "type": "cell_type", "text": [ "B cells" ], "offsets": [ [ 504, 511 ] ], "normalized": [] }, { "id": "364", "type": "protein_molecule", "text": [ "BamHI ZLF-1 gene product" ], "offsets": [ [ 594, 618 ] ], "normalized": [] }, { "id": "365", "type": "protein_molecule", "text": [ "ZEBRA" ], "offsets": [ [ 620, 625 ] ], "normalized": [] }, { "id": "366", "type": "other_name", "text": [ "RT-PCR" ], "offsets": [ [ 630, 636 ] ], "normalized": [] }, { "id": "367", "type": "protein_family_or_group", "text": [ "fusion transcript" ], "offsets": [ [ 703, 720 ] ], "normalized": [] }, { "id": "368", "type": "protein_molecule", "text": [ "RAZ" ], "offsets": [ [ 722, 725 ] ], "normalized": [] }, { "id": "369", "type": "DNA_domain_or_region", "text": [ "BZLF-1 locus" ], "offsets": [ [ 759, 771 ] ], "normalized": [] }, { "id": "370", "type": "protein_molecule", "text": [ "BZLF-1" ], "offsets": [ [ 759, 765 ] ], "normalized": [] }, { "id": "371", "type": "DNA_domain_or_region", "text": [ "BRLF-1 locus" ], "offsets": [ [ 789, 801 ] ], "normalized": [] }, { "id": "372", "type": "other_name", "text": [ "RT-PCR" ], "offsets": [ [ 819, 825 ] ], "normalized": [] }, { "id": "373", "type": "protein_molecule", "text": [ "ZEBRA protein" ], "offsets": [ [ 827, 840 ] ], "normalized": [] }, { "id": "374", "type": "protein_molecule", "text": [ "ZEBRA" ], "offsets": [ [ 827, 832 ] ], "normalized": [] }, { "id": "375", "type": "cell_type", "text": [ "thymocytes" ], "offsets": [ [ 873, 883 ] ], "normalized": [] }, { "id": "376", "type": "other_name", "text": [ "immunoprecipitation" ], "offsets": [ [ 887, 906 ] ], "normalized": [] }, { "id": "377", "type": "DNA_domain_or_region", "text": [ "EBNA-1 gene" ], "offsets": [ [ 946, 957 ] ], "normalized": [] }, { "id": "378", "type": "protein_molecule", "text": [ "EBNA-1" ], "offsets": [ [ 946, 952 ] ], "normalized": [] }, { "id": "379", "type": "cell_type", "text": [ "thymocytes" ], "offsets": [ [ 970, 980 ] ], "normalized": [] }, { "id": "380", "type": "DNA_domain_or_region", "text": [ "Fp promoter" ], "offsets": [ [ 1006, 1017 ] ], "normalized": [] }, { "id": "381", "type": "DNA_domain_or_region", "text": [ "Cp/Wp promoter" ], "offsets": [ [ 1040, 1054 ] ], "normalized": [] }, { "id": "382", "type": "cell_type", "text": [ "latently infected B cells" ], "offsets": [ [ 1072, 1097 ] ], "normalized": [] }, { "id": "383", "type": "cell_type", "text": [ "B cells" ], "offsets": [ [ 1090, 1097 ] ], "normalized": [] }, { "id": "384", "type": "protein_molecule", "text": [ "gp350/220" ], "offsets": [ [ 1120, 1129 ] ], "normalized": [] }, { "id": "385", "type": "protein_family_or_group", "text": [ "major coat protein" ], "offsets": [ [ 1135, 1153 ] ], "normalized": [] }, { "id": "386", "type": "virus", "text": [ "EBV" ], "offsets": [ [ 1157, 1160 ] ], "normalized": [] }, { "id": "387", "type": "DNA_domain_or_region", "text": [ "LMP-2A" ], "offsets": [ [ 1238, 1244 ] ], "normalized": [] }, { "id": "388", "type": "DNA_domain_or_region", "text": [ "EBER-1 loci" ], "offsets": [ [ 1248, 1259 ] ], "normalized": [] }, { "id": "389", "type": "cell_type", "text": [ "thymocytes" ], "offsets": [ [ 1272, 1282 ] ], "normalized": [] }, { "id": "390", "type": "other_name", "text": [ "EBV infection" ], "offsets": [ [ 1324, 1337 ] ], "normalized": [] }, { "id": "391", "type": "virus", "text": [ "EBV" ], "offsets": [ [ 1324, 1327 ] ], "normalized": [] }, { "id": "392", "type": "cell_type", "text": [ "thymocytes" ], "offsets": [ [ 1341, 1351 ] ], "normalized": [] }, { "id": "393", "type": "cell_type", "text": [ "B cells" ], "offsets": [ [ 1378, 1385 ] ], "normalized": [] }, { "id": "394", "type": "cell_type", "text": [ "thymocytes" ], "offsets": [ [ 1420, 1430 ] ], "normalized": [] }, { "id": "395", "type": "virus", "text": [ "virus" ], "offsets": [ [ 1468, 1473 ] ], "normalized": [] }, { "id": "396", "type": "virus", "text": [ "EBV" ], "offsets": [ [ 1501, 1504 ] ], "normalized": [] }, { "id": "397", "type": "other_name", "text": [ "linear configuration" ], "offsets": [ [ 1518, 1538 ] ], "normalized": [] }, { "id": "398", "type": "DNA_family_or_group", "text": [ "replicative genes" ], "offsets": [ [ 1550, 1567 ] ], "normalized": [] } ]

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[ { "id": "400", "type": "title", "text": [ "Identification and purification of human Stat proteins activated in response to interleukin-2." ], "offsets": [ [ 0, 94 ] ] }, { "id": "401", "type": "abstract", "text": [ "A key cytokine induced during the immune response is IL-2. Following T cell activation, the genes encoding IL-2 and the various chains of its receptor are transcriptionally induced. In turn, secreted IL-2 serves to stimulate the proliferation and differentiation of T lymphocytes. Several recent studies have implicated Jak kinases in the signaling pathway induced by IL-2. Following this lead, we set out to identify transcription factors induced in response to IL-2. Human peripheral blood lymphocytes were observed to contain several IL-2-inducible DNA binding activities. Similar activities were also observed in a transformed human lymphocyte line, termed YT. We have purified these activities and found that the principal IL-2-inducible component bears significant relatedness to a prolactin-induced transcription factor first identified in sheep mammary gland tissue. We hypothesize that activation of this protein, designated hStat5, helps govern the biological effects of IL-2 during the immune response." ], "offsets": [ [ 95, 1108 ] ] } ]

[ { "id": "402", "type": "protein_family_or_group", "text": [ "human Stat proteins" ], "offsets": [ [ 35, 54 ] ], "normalized": [] }, { "id": "403", "type": "protein_molecule", "text": [ "interleukin-2" ], "offsets": [ [ 80, 93 ] ], "normalized": [] }, { "id": "404", "type": "protein_family_or_group", "text": [ "cytokine" ], "offsets": [ [ 101, 109 ] ], "normalized": [] }, { "id": "405", "type": "other_name", "text": [ "immune response" ], "offsets": [ [ 129, 144 ] ], "normalized": [] }, { "id": "406", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 148, 152 ] ], "normalized": [] }, { "id": "407", "type": "other_name", "text": [ "T cell activation" ], "offsets": [ [ 164, 181 ] ], "normalized": [] }, { "id": "408", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 202, 206 ] ], "normalized": [] }, { "id": "409", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 295, 299 ] ], "normalized": [] }, { "id": "410", "type": "cell_type", "text": [ "T lymphocytes" ], "offsets": [ [ 361, 374 ] ], "normalized": [] }, { "id": "411", "type": "other_name", "text": [ "signaling pathway" ], "offsets": [ [ 434, 451 ] ], "normalized": [] }, { "id": "412", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 463, 467 ] ], "normalized": [] }, { "id": "413", "type": "protein_family_or_group", "text": [ "transcription factors" ], "offsets": [ [ 513, 534 ] ], "normalized": [] }, { "id": "414", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 558, 562 ] ], "normalized": [] }, { "id": "415", "type": "cell_type", "text": [ "Human peripheral blood lymphocytes" ], "offsets": [ [ 564, 598 ] ], "normalized": [] }, { "id": "416", "type": "other_name", "text": [ "IL-2-inducible DNA binding activities" ], "offsets": [ [ 632, 669 ] ], "normalized": [] }, { "id": "417", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 632, 636 ] ], "normalized": [] }, { "id": "418", "type": "cell_line", "text": [ "transformed human lymphocyte line" ], "offsets": [ [ 714, 747 ] ], "normalized": [] }, { "id": "419", "type": "cell_line", "text": [ "YT" ], "offsets": [ [ 756, 758 ] ], "normalized": [] }, { "id": "420", "type": "protein_family_or_group", "text": [ "IL-2-inducible component" ], "offsets": [ [ 823, 847 ] ], "normalized": [] }, { "id": "421", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 823, 827 ] ], "normalized": [] }, { "id": "422", "type": "protein_molecule", "text": [ "prolactin-induced transcription factor" ], "offsets": [ [ 883, 921 ] ], "normalized": [] }, { "id": "423", "type": "cell_type", "text": [ "sheep mammary gland tissue" ], "offsets": [ [ 942, 968 ] ], "normalized": [] }, { "id": "424", "type": "protein_molecule", "text": [ "hStat5" ], "offsets": [ [ 1029, 1035 ] ], "normalized": [] }, { "id": "425", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 1076, 1080 ] ], "normalized": [] }, { "id": "426", "type": "other_name", "text": [ "immune response" ], "offsets": [ [ 1092, 1107 ] ], "normalized": [] } ]

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[ { "id": "428", "type": "title", "text": [ "E2F-1 and a cyclin-like DNA repair enzyme, uracil-DNA glycosylase, provide evidence for an autoregulatory mechanism for transcription." ], "offsets": [ [ 0, 134 ] ] }, { "id": "429", "type": "abstract", "text": [ "The cell cycle-dependent transcription factor, E2F-1, regulates the cyclin-like species of the DNA repair enzyme uracil-DNA glycosylase (UDG) gene in human osteosarcoma (Saos-2) cells. We demonstrate, through the deletion of the human UDG promoter sequences, that expression of E2F-1 activates the UDG promoter through several E2F sites. The major putative downstream site for E2F, located in the first exon, serves as a target for E2F-1/DP1 complex binding in vitro. We also provide evidence for the functional relationship between the cyclin-like UDG gene product and E2F. High levels of UDG expression in a transient transfection assay result in the down-regulation of transcriptional activity through elements specific for E2F-mediated transcription. Overexpression of UDG in Saos 2 cells was observed to delay growth late in G1 phase and transiently arrest these cells from progressing into the S phase. This hypothetical model integrates one mechanism of DNA repair with the cell cycle control of gene transcription, likely through E2F. This implicates E2F as a multifunctional target for proteins and enzymes, possibly, responsive to DNA damage through the negative effect of UDG on E2F-mediated transcriptional activity." ], "offsets": [ [ 135, 1363 ] ] } ]

[ { "id": "430", "type": "protein_molecule", "text": [ "E2F-1" ], "offsets": [ [ 0, 5 ] ], "normalized": [] }, { "id": "431", "type": "protein_family_or_group", "text": [ "cyclin-like DNA repair enzyme" ], "offsets": [ [ 12, 41 ] ], "normalized": [] }, { "id": "432", "type": "protein_molecule", "text": [ "uracil-DNA glycosylase" ], "offsets": [ [ 43, 65 ] ], "normalized": [] }, { "id": "433", "type": "other_name", "text": [ "autoregulatory mechanism for transcription" ], "offsets": [ [ 91, 133 ] ], "normalized": [] }, { "id": "434", "type": "protein_family_or_group", "text": [ "cell cycle-dependent transcription factor" ], "offsets": [ [ 139, 180 ] ], "normalized": [] }, { "id": "435", "type": "protein_molecule", "text": [ "E2F-1" ], "offsets": [ [ 182, 187 ] ], "normalized": [] }, { "id": "436", "type": "protein_family_or_group", "text": [ "cyclin" ], "offsets": [ [ 203, 209 ] ], "normalized": [] }, { "id": "437", "type": "protein_family_or_group", "text": [ "DNA repair enzyme" ], "offsets": [ [ 230, 247 ] ], "normalized": [] }, { "id": "438", "type": "DNA_domain_or_region", "text": [ "uracil-DNA glycosylase (UDG) gene" ], "offsets": [ [ 248, 281 ] ], "normalized": [] }, { "id": "439", "type": "protein_molecule", "text": [ "uracil-DNA glycosylase" ], "offsets": [ [ 248, 270 ] ], "normalized": [] }, { "id": "440", "type": "protein_molecule", "text": [ "UDG" ], "offsets": [ [ 272, 275 ] ], "normalized": [] }, { "id": "441", "type": "cell_line", "text": [ "human osteosarcoma (Saos-2) cells" ], "offsets": [ [ 285, 318 ] ], "normalized": [] }, { "id": "442", "type": "cell_line", "text": [ "Saos-2" ], "offsets": [ [ 305, 311 ] ], "normalized": [] }, { "id": "443", "type": "DNA_domain_or_region", "text": [ "human UDG promoter sequences" ], "offsets": [ [ 364, 392 ] ], "normalized": [] }, { "id": "444", "type": "protein_molecule", "text": [ "UDG" ], "offsets": [ [ 370, 373 ] ], "normalized": [] }, { "id": "445", "type": "protein_molecule", "text": [ "E2F-1" ], "offsets": [ [ 413, 418 ] ], "normalized": [] }, { "id": "446", "type": "DNA_domain_or_region", "text": [ "UDG promoter" ], "offsets": [ [ 370, 382 ] ], "normalized": [] }, { "id": "447", "type": "protein_molecule", "text": [ "UDG" ], "offsets": [ [ 433, 436 ] ], "normalized": [] }, { "id": "448", "type": "DNA_domain_or_region", "text": [ "E2F sites" ], "offsets": [ [ 462, 471 ] ], "normalized": [] }, { "id": "449", "type": "protein_family_or_group", "text": [ "E2F" ], "offsets": [ [ 413, 416 ] ], "normalized": [] }, { "id": "450", "type": "DNA_domain_or_region", "text": [ "major putative downstream site" ], "offsets": [ [ 477, 507 ] ], "normalized": [] }, { "id": "451", "type": "protein_family_or_group", "text": [ "E2F" ], "offsets": [ [ 512, 515 ] ], "normalized": [] }, { "id": "452", "type": "DNA_domain_or_region", "text": [ "first exon" ], "offsets": [ [ 532, 542 ] ], "normalized": [] }, { "id": "453", "type": "protein_complex", "text": [ "E2F-1/DP1 complex" ], "offsets": [ [ 567, 584 ] ], "normalized": [] }, { "id": "454", "type": "protein_molecule", "text": [ "cyclin-like UDG gene product" ], "offsets": [ [ 672, 700 ] ], "normalized": [] }, { "id": "455", "type": "protein_molecule", "text": [ "UDG" ], "offsets": [ [ 684, 687 ] ], "normalized": [] }, { "id": "456", "type": "protein_family_or_group", "text": [ "E2F" ], "offsets": [ [ 705, 708 ] ], "normalized": [] }, { "id": "457", "type": "other_name", "text": [ "UDG expression" ], "offsets": [ [ 725, 739 ] ], "normalized": [] }, { "id": "458", "type": "protein_molecule", "text": [ "UDG" ], "offsets": [ [ 725, 728 ] ], "normalized": [] }, { "id": "459", "type": "other_name", "text": [ "transient transfection assay" ], "offsets": [ [ 745, 773 ] ], "normalized": [] }, { "id": "460", "type": "other_name", "text": [ "down-regulation" ], "offsets": [ [ 788, 803 ] ], "normalized": [] }, { "id": "461", "type": "other_name", "text": [ "transcriptional activity" ], "offsets": [ [ 807, 831 ] ], "normalized": [] }, { "id": "462", "type": "DNA_domain_or_region", "text": [ "elements" ], "offsets": [ [ 840, 848 ] ], "normalized": [] }, { "id": "463", "type": "other_name", "text": [ "E2F-mediated transcription" ], "offsets": [ [ 862, 888 ] ], "normalized": [] }, { "id": "464", "type": "protein_family_or_group", "text": [ "E2F" ], "offsets": [ [ 862, 865 ] ], "normalized": [] }, { "id": "465", "type": "other_name", "text": [ "Overexpression" ], "offsets": [ [ 890, 904 ] ], "normalized": [] }, { "id": "466", "type": "protein_molecule", "text": [ "UDG" ], "offsets": [ [ 908, 911 ] ], "normalized": [] }, { "id": "467", "type": "cell_line", "text": [ "Saos 2 cells" ], "offsets": [ [ 915, 927 ] ], "normalized": [] }, { "id": "468", "type": "other_name", "text": [ "G1 phase" ], "offsets": [ [ 965, 973 ] ], "normalized": [] }, { "id": "469", "type": "other_name", "text": [ "S phase" ], "offsets": [ [ 1035, 1042 ] ], "normalized": [] }, { "id": "470", "type": "other_name", "text": [ "DNA repair" ], "offsets": [ [ 1096, 1106 ] ], "normalized": [] }, { "id": "471", "type": "other_name", "text": [ "cell cycle control" ], "offsets": [ [ 1116, 1134 ] ], "normalized": [] }, { "id": "472", "type": "other_name", "text": [ "gene transcription" ], "offsets": [ [ 1138, 1156 ] ], "normalized": [] }, { "id": "473", "type": "protein_family_or_group", "text": [ "E2F" ], "offsets": [ [ 1173, 1176 ] ], "normalized": [] }, { "id": "474", "type": "protein_family_or_group", "text": [ "E2F" ], "offsets": [ [ 1194, 1197 ] ], "normalized": [] }, { "id": "475", "type": "other_name", "text": [ "DNA damage" ], "offsets": [ [ 1276, 1286 ] ], "normalized": [] }, { "id": "476", "type": "protein_molecule", "text": [ "UDG" ], "offsets": [ [ 1318, 1321 ] ], "normalized": [] }, { "id": "477", "type": "other_name", "text": [ "E2F-mediated transcriptional activity" ], "offsets": [ [ 1325, 1362 ] ], "normalized": [] }, { "id": "478", "type": "protein_family_or_group", "text": [ "E2F" ], "offsets": [ [ 1325, 1328 ] ], "normalized": [] } ]

[]

[]

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[ { "id": "480", "type": "title", "text": [ "Cellular and molecular mechanisms of IFN-gamma production induced by IL-2 and IL-12 in a human NK cell line." ], "offsets": [ [ 0, 108 ] ] }, { "id": "481", "type": "abstract", "text": [ "Interferon-gamma (IFN-gamma) is an important immunoregulatory protein produced predominantly by T cells and large granular lymphocytes (LGL) in response to different extracellular signals. In particular, two interleukins (ILs), IL-2 and IL-12, have been shown to be potent inducers of IFN-gamma gene expression in both T cells and LGL. Although it has been reported that there are some T cell lines that produce IFN-gamma in response to IL-2 and IL-12 stimulation, there has as yet been no report of a natural killer (NK) cell line that responds in a similar manner. In this report we present evidence that the cell line NK3.3 derived from human NK cells, responds to both IL-2 and IL-12, as measured by increases in IFN-gamma and granulocyte-macrophage colony-stimulating factor (GM-CSF) cytoplasmic mRNA and protein expression. In addition, when used together IL-2 and IL-12 synergized in the induction of IFN-gamma and GM-CSF and this synergy was attributed to an increased accumulation and stability of the IFN-gamma and GM-CSF mRNAs. To investigate the signaling pathways involved in the gene induction, five inhibitors, cyclosporin A (CsA), transforming growth factor-beta, cycloheximide, genistein, and staurosporine A, were used in analyzing the effects of IL-2 and IL-12 on NK3.3 cells. The results suggest that activation of protein kinase C, but not new protein synthesis, is required for IL-2 induction of IFN-gamma and GM-CSF cytoplasmic mRNA. In contrast, IL-12 induction of IFN-gamma cytoplasmic mRNA appears to only partially depend on activation of protein kinase C. Furthermore, both transforming growth factor-beta and genistein, a tyrosine kinase inhibitor, could suppress IL-2 and IL-12 signaling but CsA was generally inactive. It also was observed that suppression of cytokine gene expression by these agents was independent of the inhibition of proliferation. In addition, IL-2 but not IL-12 induced nuclear factors NF-kappa B and AP1, and regulation of the nuclear levels of these two DNA binding protein complexes is correlated with IFN-gamma and GM-CSF gene expression. These data indicate that IL-2 and IL-12 may have distinct signaling pathways leading to the induction of IFN-gamma and GM-CSF gene expression, and that the NK3.3 cell line may serve as a novel model for dissecting the biochemical and molecular events involved in these pathways." ], "offsets": [ [ 109, 2484 ] ] } ]

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"type": "protein_family_or_group", "text": [ "ILs" ], "offsets": [ [ 331, 334 ] ], "normalized": [] }, { "id": "500", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 337, 341 ] ], "normalized": [] }, { "id": "501", "type": "protein_molecule", "text": [ "IL-12" ], "offsets": [ [ 346, 351 ] ], "normalized": [] }, { "id": "502", "type": "other_name", "text": [ "IFN-gamma gene expression" ], "offsets": [ [ 394, 419 ] ], "normalized": [] }, { "id": "503", "type": "protein_molecule", "text": [ "IFN-gamma" ], "offsets": [ [ 394, 403 ] ], "normalized": [] }, { "id": "504", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 428, 435 ] ], "normalized": [] }, { "id": "505", "type": "cell_type", "text": [ "LGL" ], "offsets": [ [ 440, 443 ] ], "normalized": [] }, { "id": "506", "type": "cell_line", "text": [ "T cell lines" ], "offsets": [ [ 495, 507 ] ], "normalized": [] }, { "id": "507", "type": "protein_molecule", "text": [ "IFN-gamma" ], "offsets": [ [ 521, 530 ] ], "normalized": [] }, { "id": "508", "type": "(AND other_name other_name)", "text": [ "IL-2 and IL-12 stimulation" ], "offsets": [ [ 546, 572 ] ], "normalized": [] }, { "id": "509", "type": "", "text": [ "IL-2" ], "offsets": [ [ 546, 550 ] ], "normalized": [] }, { "id": "510", "type": "", "text": [ "IL-12" ], "offsets": [ [ 555, 560 ] ], "normalized": [] }, { "id": "511", "type": "", "text": [ "stimulation" ], "offsets": [ [ 561, 572 ] ], "normalized": [] }, { "id": "512", "type": "cell_line", "text": [ "natural killer (NK) cell line" ], "offsets": [ [ 611, 640 ] ], "normalized": [] }, { "id": "513", "type": "cell_line", "text": [ "cell line NK3.3" ], "offsets": [ [ 720, 735 ] ], "normalized": [] }, { "id": "514", "type": "cell_type", "text": [ "human NK cells" ], "offsets": [ [ 749, 763 ] ], "normalized": [] }, { "id": "515", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 782, 786 ] ], "normalized": [] }, { "id": "516", "type": "protein_molecule", "text": [ "IL-12" ], "offsets": [ [ 791, 796 ] ], "normalized": [] }, { "id": "517", "type": "protein_molecule", "text": [ "IFN-gamma" ], "offsets": [ [ 826, 835 ] ], "normalized": [] }, { "id": "518", "type": "protein_molecule", "text": [ "granulocyte-macrophage colony-stimulating factor" ], "offsets": [ [ 840, 888 ] ], "normalized": [] }, { "id": "519", "type": "protein_molecule", "text": [ "GM-CSF" ], "offsets": [ [ 890, 896 ] ], "normalized": [] }, { "id": "520", "type": "(AND other_name other_name)", "text": [ "cytoplasmic mRNA and protein expression" ], "offsets": [ [ 898, 937 ] ], "normalized": [] }, { "id": "521", "type": "", "text": [ "cytoplasmic" ], "offsets": [ [ 898, 909 ] ], "normalized": [] }, { "id": "522", "type": "", "text": [ "mRNA" ], "offsets": [ [ 910, 914 ] ], "normalized": [] }, { "id": "523", "type": "", "text": [ "protein" ], "offsets": [ [ 919, 926 ] ], "normalized": [] }, { "id": "524", "type": "", "text": [ "expression" ], "offsets": [ [ 927, 937 ] ], "normalized": [] }, { 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"GM-CSF" ], "offsets": [ [ 1134, 1140 ] ], "normalized": [] }, { "id": "534", "type": "other_organic_compound", "text": [ "cyclosporin A" ], "offsets": [ [ 1235, 1248 ] ], "normalized": [] }, { "id": "535", "type": "other_organic_compound", "text": [ "CsA" ], "offsets": [ [ 1250, 1253 ] ], "normalized": [] }, { "id": "536", "type": "protein_molecule", "text": [ "transforming growth factor-beta" ], "offsets": [ [ 1256, 1287 ] ], "normalized": [] }, { "id": "537", "type": "other_organic_compound", "text": [ "cycloheximide" ], "offsets": [ [ 1289, 1302 ] ], "normalized": [] }, { "id": "538", "type": "other_organic_compound", "text": [ "genistein" ], "offsets": [ [ 1304, 1313 ] ], "normalized": [] }, { "id": "539", "type": "other_organic_compound", "text": [ "staurosporine A" ], "offsets": [ [ 1319, 1334 ] ], "normalized": [] }, { "id": "540", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 1374, 1378 ] ], "normalized": [] }, { "id": "541", "type": "protein_molecule", "text": [ "IL-12" ], "offsets": [ [ 1383, 1388 ] ], "normalized": [] }, { "id": "542", "type": "cell_line", "text": [ "NK3.3 cells" ], "offsets": [ [ 1392, 1403 ] ], "normalized": [] }, { "id": "543", "type": "protein_molecule", "text": [ "protein kinase C" ], "offsets": [ [ 1444, 1460 ] ], "normalized": [] }, { "id": "544", "type": "other_name", "text": [ "new protein synthesis" ], "offsets": [ [ 1470, 1491 ] ], "normalized": [] }, { "id": "545", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 1509, 1513 ] ], "normalized": [] }, { "id": "546", "type": "(AND RNA_molecule RNA_molecule)", "text": [ "IFN-gamma and GM-CSF cytoplasmic mRNA" ], "offsets": [ [ 1527, 1564 ] ], "normalized": [] }, { "id": "547", "type": "", "text": [ "IFN-gamma" ], "offsets": [ [ 1527, 1536 ] ], "normalized": [] }, { "id": "548", "type": "", "text": [ "GM-CSF" ], "offsets": [ [ 1541, 1547 ] ], "normalized": [] }, { "id": "549", "type": "", "text": [ "cytoplasmic mRNA" ], "offsets": [ [ 1548, 1564 ] ], "normalized": [] }, { "id": "550", "type": "other_name", "text": [ "IL-12 induction" ], "offsets": [ [ 1579, 1594 ] ], "normalized": [] }, { "id": "551", "type": "protein_molecule", "text": [ "IL-12" ], "offsets": [ [ 1579, 1584 ] ], "normalized": [] }, { "id": "552", "type": "RNA_molecule", "text": [ "IFN-gamma cytoplasmic mRNA" ], "offsets": [ [ 1598, 1624 ] ], "normalized": [] }, { "id": "553", "type": "protein_molecule", "text": [ "IFN-gamma" ], "offsets": [ [ 1598, 1607 ] ], "normalized": [] }, { "id": "554", "type": "protein_molecule", "text": [ "protein kinase C" ], "offsets": [ [ 1675, 1691 ] ], "normalized": [] }, { "id": "555", "type": "protein_molecule", "text": [ "transforming growth factor-beta" ], "offsets": [ [ 1711, 1742 ] ], "normalized": [] }, { "id": "556", "type": "other_organic_compound", "text": [ "genistein" ], "offsets": [ [ 1747, 1756 ] ], "normalized": [] }, { "id": "557", "type": "other_name", "text": [ "tyrosine kinase inhibitor" ], "offsets": [ [ 1760, 1785 ] ], "normalized": [] }, { "id": "558", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 1802, 1806 ] ], "normalized": [] }, { "id": "559", "type": "protein_molecule", "text": [ "IL-12" ], "offsets": [ [ 1811, 1816 ] ], "normalized": [] }, { "id": "560", "type": "other_organic_compound", "text": [ "CsA" ], "offsets": [ [ 1831, 1834 ] ], "normalized": [] }, { "id": "561", "type": "other_name", "text": [ "cytokine gene expression" ], "offsets": [ [ 1900, 1924 ] ], "normalized": [] }, { "id": "562", "type": "DNA_family_or_group", "text": [ "cytokine gene" ], "offsets": [ [ 1900, 1913 ] ], "normalized": [] }, { "id": "563", "type": "other_name", "text": [ "inhibition of proliferation" ], "offsets": [ [ 1964, 1991 ] ], "normalized": [] }, { "id": "564", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 2006, 2010 ] ], "normalized": [] }, { "id": "565", "type": "protein_molecule", "text": [ "IL-12" ], "offsets": [ [ 2019, 2024 ] ], "normalized": [] }, { "id": "566", "type": "protein_family_or_group", "text": [ "nuclear factors" ], "offsets": [ [ 2033, 2048 ] ], "normalized": [] }, { "id": "567", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 2049, 2059 ] ], "normalized": [] }, { "id": "568", "type": "protein_molecule", "text": [ "AP1" ], "offsets": [ [ 2064, 2067 ] ], "normalized": [] }, { "id": "569", "type": "other_name", "text": [ "nuclear levels" ], "offsets": [ [ 2091, 2105 ] ], "normalized": [] }, { "id": "570", "type": "protein_complex", "text": [ "DNA binding protein complexes" ], "offsets": [ [ 2119, 2148 ] ], "normalized": [] }, { "id": "571", "type": "(AND other_name other_name)", "text": [ "IFN-gamma and GM-CSF gene expression" ], "offsets": [ [ 2168, 2204 ] ], "normalized": [] }, { "id": "572", "type": "", "text": [ "IFN-gamma" ], "offsets": [ [ 2168, 2177 ] ], "normalized": [] }, { "id": "573", "type": "", "text": [ "GM-CSF" ], "offsets": [ [ 2182, 2188 ] ], "normalized": [] }, { "id": "574", "type": "", "text": [ "gene expression" ], "offsets": [ [ 2189, 2204 ] ], "normalized": [] }, { "id": "575", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 2231, 2235 ] ], "normalized": [] }, { "id": "576", "type": "protein_molecule", "text": [ "IL-12" ], "offsets": [ [ 2240, 2245 ] ], "normalized": [] }, { "id": "577", "type": "other_name", "text": [ "signaling pathways" ], "offsets": [ [ 2264, 2282 ] ], "normalized": [] }, { "id": "578", "type": "protein_molecule", "text": [ "IFN-gamma" ], "offsets": [ [ 2311, 2320 ] ], "normalized": [] }, { "id": "579", "type": "other_name", "text": [ "GM-CSF gene expression" ], "offsets": [ [ 2325, 2347 ] ], "normalized": [] }, { "id": "580", "type": "protein_molecule", "text": [ "GM-CSF" ], "offsets": [ [ 2325, 2331 ] ], "normalized": [] }, { "id": "581", "type": "cell_line", "text": [ "NK3.3 cell line" ], "offsets": [ [ 2362, 2377 ] ], "normalized": [] }, { "id": "582", "type": "other_name", "text": [ "biochemical and molecular events" ], "offsets": [ [ 2424, 2456 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "584", "type": "title", "text": [ "A functional T-cell receptor signaling pathway is required for p95vav activity." ], "offsets": [ [ 0, 79 ] ] }, { "id": "585", "type": "abstract", "text": [ "Stimulation of the T-cell antigen receptor (TCR) induces activation of multiple tyrosine kinases, resulting in phosphorylation of numerous intracellular substrates. One substrate is p95vav, which is expressed exclusively in hematopoietic and trophoblast cells. It contains a number of structural motifs, including Src homology 2, Src homology 3, and pleckstrin homology domains and a putative guanine nucleotide exchange domain. The role of p95vav in TCR-mediated signaling processes is unclear. Here, we show that overexpression of p95vav alone in Jurkat T cells leads to activation of the nuclear factors, including NFAT, involved in interleukin-2 expression. Furthermore, p95vav synergizes with TCR stimulation in inducing NFAT- and interleukin-2-dependent transcription. In contrast, NFAT activation by a G-protein-coupled receptor is not modulated by p95vav overexpression, suggesting that the effect is specific to the TCR signaling pathways. Although removal of the first 67 amino acids of p95vav activates its transforming potential in NIH 3T3 cells, this region appears to be required for its function in T cells. We further demonstrate that the p95vav-induced NFAT activation is not mimicked by Ras activation, though its function is dependent upon Ras and Raf. Furthermore, the activating function of p95vav is blocked by FK506, suggesting that its activity also depends on calcineurin. To further dissect p95vav involvement in TCR signaling, we analyzed various Jurkat mutants deficient in TCR signaling function or TCR expression and showed that an intact TCR signaling pathway is required for p95vav to function. However, overexpression of p95vav does not appear to influence TCR-induced protein tyrosine phosphorylation or increases in cytoplasmic free calcium. Taken together, our data suggest that p95vav plays an important role at an yet unidentified proximal position in the TCR signaling cascade." ], "offsets": [ [ 80, 1996 ] ] } ]

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"type": "other_organic_compound", "text": [ "intracellular substrates" ], "offsets": [ [ 219, 243 ] ], "normalized": [] }, { "id": "595", "type": "protein_molecule", "text": [ "p95vav" ], "offsets": [ [ 262, 268 ] ], "normalized": [] }, { "id": "596", "type": "(AND cell_type cell_type)", "text": [ "hematopoietic and trophoblast cells" ], "offsets": [ [ 304, 339 ] ], "normalized": [] }, { "id": "597", "type": "", "text": [ "hematopoietic" ], "offsets": [ [ 304, 317 ] ], "normalized": [] }, { "id": "598", "type": "", "text": [ "trophoblast" ], "offsets": [ [ 322, 333 ] ], "normalized": [] }, { "id": "599", "type": "", "text": [ "cells" ], "offsets": [ [ 334, 339 ] ], "normalized": [] }, { "id": "600", "type": "protein_substructure", "text": [ "structural motifs" ], "offsets": [ [ 365, 382 ] ], "normalized": [] }, { "id": "601", "type": "protein_domain_or_region", "text": [ "Src homology 2, Src homology 3, and pleckstrin homology domains" ], "offsets": [ [ 394, 457 ] ], "normalized": [] }, { "id": "602", "type": "protein_domain_or_region", "text": [ "Src homology 2" ], "offsets": [ [ 394, 408 ] ], "normalized": [] }, { "id": "603", "type": "protein_domain_or_region", "text": [ "Src homology 3" ], "offsets": [ [ 410, 424 ] ], "normalized": [] }, { "id": "604", "type": "protein_domain_or_region", "text": [ "pleckstrin homology domains" ], "offsets": [ [ 430, 457 ] ], "normalized": [] }, { "id": "605", "type": "protein_domain_or_region", "text": [ "putative guanine nucleotide exchange domain" ], "offsets": [ [ 464, 507 ] ], "normalized": [] }, { "id": "606", "type": "protein_molecule", "text": [ "p95vav" ], "offsets": [ [ 521, 527 ] ], "normalized": [] }, { "id": "607", "type": "other_name", "text": [ "TCR-mediated signaling processes" ], "offsets": [ [ 531, 563 ] ], "normalized": [] }, { "id": "608", "type": "protein_molecule", "text": [ "TCR" ], "offsets": [ [ 531, 534 ] ], "normalized": [] }, { "id": "609", "type": "protein_molecule", "text": [ "p95vav" ], "offsets": [ [ 613, 619 ] ], "normalized": [] }, { "id": "610", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 636, 643 ] ], "normalized": [] }, { "id": "611", "type": "protein_family_or_group", "text": [ "nuclear factors" ], "offsets": [ [ 671, 686 ] ], "normalized": [] }, { "id": "612", "type": "protein_family_or_group", "text": [ "NFAT" ], "offsets": [ [ 698, 702 ] ], "normalized": [] }, { "id": "613", "type": "other_name", "text": [ "interleukin-2 expression" ], "offsets": [ [ 716, 740 ] ], "normalized": [] }, { "id": "614", "type": "protein_molecule", "text": [ "interleukin-2" ], "offsets": [ [ 716, 729 ] ], "normalized": [] }, { "id": "615", "type": "protein_molecule", "text": [ "p95vav" ], "offsets": [ [ 755, 761 ] ], "normalized": [] }, { "id": "616", "type": "other_name", "text": [ "TCR stimulation" ], "offsets": [ [ 778, 793 ] ], "normalized": [] }, { "id": "617", "type": "protein_molecule", "text": [ "TCR" ], "offsets": [ [ 778, 781 ] ], "normalized": [] }, { "id": "618", "type": "(AND other_name other_name)", "text": [ "NFAT- and interleukin-2-dependent transcription" ], "offsets": [ [ 806, 853 ] ], "normalized": [] }, { "id": "619", "type": "", "text": [ "NFAT-" ], "offsets": [ [ 806, 811 ] ], "normalized": [] }, { "id": "620", "type": "", "text": [ "interleukin-2-" ], "offsets": [ [ 816, 830 ] ], "normalized": [] }, { "id": "621", "type": "", "text": [ "dependent transcription" ], "offsets": [ [ 830, 853 ] ], "normalized": [] }, { "id": "622", "type": "other_name", "text": [ "NFAT activation" ], "offsets": [ [ 868, 883 ] ], "normalized": [] }, { "id": "623", "type": "protein_family_or_group", "text": [ "NFAT" ], "offsets": [ [ 868, 872 ] ], "normalized": [] }, { "id": "624", "type": "protein_family_or_group", "text": [ "G-protein-coupled receptor" ], "offsets": [ [ 889, 915 ] ], "normalized": [] }, { "id": "625", "type": "other_name", "text": [ "p95vav overexpression" ], "offsets": [ [ 936, 957 ] ], "normalized": [] }, { "id": "626", "type": "protein_molecule", "text": [ "p95vav" ], "offsets": [ [ 936, 942 ] ], "normalized": [] }, { "id": "627", "type": "other_name", "text": [ "TCR signaling pathways" ], "offsets": [ [ 1005, 1027 ] ], "normalized": [] }, { "id": "628", "type": "protein_molecule", "text": [ "TCR" ], "offsets": [ [ 1005, 1008 ] ], "normalized": [] }, { "id": "629", "type": "other_name", "text": [ "signaling pathways" ], "offsets": [ [ 1009, 1027 ] ], "normalized": [] }, { "id": "630", "type": "protein_domain_or_region", "text": [ "first 67 amino acids" ], "offsets": [ [ 1053, 1073 ] ], "normalized": [] }, { "id": "631", "type": "protein_molecule", "text": [ "p95vav" ], "offsets": [ [ 1077, 1083 ] ], "normalized": [] }, { "id": "632", "type": "other_name", "text": [ "transforming potential" ], "offsets": [ [ 1098, 1120 ] ], "normalized": [] }, { "id": "633", "type": "cell_line", "text": [ "NIH 3T3 cells" ], "offsets": [ [ 1124, 1137 ] ], "normalized": [] }, { "id": "634", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 1194, 1201 ] ], "normalized": [] }, { "id": "635", "type": "other_name", "text": [ "p95vav-induced NFAT activation" ], "offsets": [ [ 1235, 1265 ] ], "normalized": [] }, { "id": "636", "type": "protein_molecule", "text": [ "p95vav" ], "offsets": [ [ 1235, 1241 ] ], "normalized": [] }, { "id": "637", "type": "protein_family_or_group", "text": [ "NFAT" ], "offsets": [ [ 1250, 1254 ] ], "normalized": [] }, { "id": "638", "type": "other_name", "text": [ "Ras activation" ], "offsets": [ [ 1285, 1299 ] ], "normalized": [] }, { "id": "639", "type": "protein_family_or_group", "text": [ "Ras" ], "offsets": [ [ 1285, 1288 ] ], "normalized": [] }, { "id": "640", "type": "protein_family_or_group", "text": [ "Ras" ], "offsets": [ [ 1339, 1342 ] ], "normalized": [] }, { "id": "641", "type": "protein_family_or_group", "text": [ "Raf" ], "offsets": [ [ 1347, 1350 ] ], "normalized": [] }, { "id": "642", "type": "other_name", "text": [ "activating function" ], "offsets": [ [ 1369, 1388 ] ], "normalized": [] }, { "id": "643", "type": "protein_molecule", "text": [ "p95vav" ], "offsets": [ [ 1392, 1398 ] ], "normalized": [] }, { "id": "644", "type": "other_organic_compound", "text": [ "FK506" ], "offsets": [ [ 1413, 1418 ] ], "normalized": [] }, { "id": "645", "type": "protein_molecule", "text": [ "calcineurin" ], "offsets": [ [ 1465, 1476 ] ], "normalized": [] }, { "id": "646", "type": "other_name", "text": [ "p95vav involvement" ], "offsets": [ [ 1497, 1515 ] ], "normalized": [] }, { "id": "647", "type": "protein_molecule", "text": [ "p95vav" ], "offsets": [ [ 1497, 1503 ] ], "normalized": [] }, { "id": "648", "type": "other_name", "text": [ "TCR signaling" ], "offsets": [ [ 1519, 1532 ] ], "normalized": [] }, { "id": "649", "type": "protein_molecule", "text": [ "TCR" ], "offsets": [ [ 1519, 1522 ] ], "normalized": [] }, { "id": "650", "type": "cell_line", "text": [ "Jurkat mutants" ], "offsets": [ [ 1554, 1568 ] ], "normalized": [] }, { "id": "651", "type": "other_name", "text": [ "TCR signaling function" ], "offsets": [ [ 1582, 1604 ] ], "normalized": [] }, { "id": "652", "type": "protein_molecule", "text": [ "TCR" ], "offsets": [ [ 1582, 1585 ] ], "normalized": [] }, { "id": "653", "type": "other_name", "text": [ "TCR expression" ], "offsets": [ [ 1608, 1622 ] ], "normalized": [] }, { "id": "654", "type": "protein_molecule", "text": [ "TCR" ], "offsets": [ [ 1608, 1611 ] ], "normalized": [] }, { "id": "655", "type": "other_name", "text": [ "TCR signaling pathway" ], "offsets": [ [ 1649, 1670 ] ], "normalized": [] }, { "id": "656", "type": "protein_molecule", "text": [ "TCR" ], "offsets": [ [ 1649, 1652 ] ], "normalized": [] }, { "id": "657", "type": "protein_molecule", "text": [ "p95vav" ], "offsets": [ [ 1687, 1693 ] ], "normalized": [] }, { "id": "658", "type": "other_name", "text": [ "overexpression" ], "offsets": [ [ 1716, 1730 ] ], "normalized": [] }, { "id": "659", "type": "protein_molecule", "text": [ "p95vav" ], "offsets": [ [ 1734, 1740 ] ], "normalized": [] }, { "id": "660", "type": "other_name", "text": [ "TCR-induced protein tyrosine phosphorylation" ], "offsets": [ [ 1770, 1814 ] ], "normalized": [] }, { "id": "661", "type": "protein_molecule", "text": [ "TCR" ], "offsets": [ [ 1770, 1773 ] ], "normalized": [] }, { "id": "662", "type": "amino_acid_monomer", "text": [ "tyrosine" ], "offsets": [ [ 1790, 1798 ] ], "normalized": [] }, { "id": "663", "type": "other_name", "text": [ "phosphorylation" ], "offsets": [ [ 1799, 1814 ] ], "normalized": [] }, { "id": "664", "type": "atom", "text": [ "cytoplasmic free calcium" ], "offsets": [ [ 1831, 1855 ] ], "normalized": [] }, { "id": "665", "type": "protein_molecule", "text": [ "p95vav" ], "offsets": [ [ 1895, 1901 ] ], "normalized": [] }, { "id": "666", "type": "other_name", "text": [ "unidentified proximal position" ], "offsets": [ [ 1936, 1966 ] ], "normalized": [] }, { "id": "667", "type": "other_name", "text": [ "TCR signaling cascade" ], "offsets": [ [ 1974, 1995 ] ], "normalized": [] }, { "id": "668", "type": "protein_molecule", "text": [ "TCR" ], "offsets": [ [ 1974, 1977 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "670", "type": "title", "text": [ "Positive and negative regulation of granulocyte-macrophage colony-stimulating factor promoter activity by AML1-related transcription factor, PEBP2." ], "offsets": [ [ 0, 147 ] ] }, { "id": "671", "type": "abstract", "text": [ "The granulocyte-macrophage colony-stimulating factor (GM-CSF) gene promoter contains a consensus sequence for the polyomavirus enhancer binding-protein 2 (PEBP2) transcription factor, which consists of alpha and beta subunits. There are at least two genes, alpha A and alpha B, encoding the alpha subunit. alpha B is the mouse homologue of human AML1 gene detected at the breakpoints of t(8;21) and t(3;21) myeloid leukemias. We examined alpha A1 (an alpha A-gene product) and alpha B1 and alpha B2 (two alpha B-encoded isomers) for their effects on the GM-CSF promoter. PEBP2 alpha A1, alpha B1, and alpha B2 proteins bound the PEBP2 site within the mouse GM-CSF promoter. PEBP2 alpha A1 and alpha B1 enhanced the expression of the GM-CSF promoter-driven reporter plasmid in unstimulated and 12-O-tetradecanoylphorbol 13-acetate/phytohemagglutinin-stimulated human Jurkat T cells. In contrast, the promoter activity was suppressed by alpha B2. Coexpression of alpha B1 and alpha B2 showed that the promoter activity could be determined by the alpha B1/alpha B2 ratio. Jurkat cell extract contained PEBP2 site-binding protein(s) that cross-reacted with antimouse alpha A1 antibodies. Northern blot analysis indicated the expression of human PEBP2 alpha A, alpha B (AML1), and beta genes in Jurkat cells. Although further studies are required to determine the precise role of PEBP2 in the GM-CSF promoter activity, the present findings suggested the importance of the relative ratio of different PEBP2 isoforms in regulating the levels of the promoter activity." ], "offsets": [ [ 148, 1708 ] ] } ]

[ { "id": "672", "type": "(AND other_name other_name)", "text": [ "Positive and negative regulation" ], "offsets": [ [ 0, 32 ] ], "normalized": [] }, { "id": "673", "type": "", "text": [ "Positive" ], "offsets": [ [ 0, 8 ] ], "normalized": [] }, { "id": "674", "type": "", "text": [ "negative" ], "offsets": [ [ 13, 21 ] ], "normalized": [] }, { "id": "675", "type": "", "text": [ "regulation" ], "offsets": [ [ 22, 32 ] ], "normalized": [] }, { "id": "676", "type": "other_name", "text": [ "granulocyte-macrophage colony-stimulating factor promoter activity" ], "offsets": [ [ 36, 102 ] ], "normalized": [] }, { "id": "677", "type": "protein_molecule", "text": [ "granulocyte-macrophage colony-stimulating factor" ], "offsets": [ [ 36, 84 ] ], "normalized": [] }, { "id": "678", "type": "protein_molecule", "text": [ "AML1-related transcription factor" ], "offsets": [ [ 106, 139 ] ], "normalized": [] }, { "id": "679", "type": "protein_molecule", "text": [ "PEBP2" ], "offsets": [ [ 141, 146 ] ], "normalized": [] }, { "id": "680", "type": "DNA_domain_or_region", "text": [ "granulocyte-macrophage colony-stimulating factor (GM-CSF) gene promoter" ], "offsets": [ [ 152, 223 ] ], "normalized": [] }, { "id": "681", "type": "protein_molecule", "text": [ "granulocyte-macrophage colony-stimulating factor" ], "offsets": [ [ 152, 200 ] ], "normalized": [] }, { "id": "682", "type": "protein_molecule", "text": [ "GM-CSF" ], "offsets": [ [ 202, 208 ] ], "normalized": [] }, { "id": "683", "type": "protein_molecule", "text": [ "polyomavirus enhancer binding-protein 2 (PEBP2) transcription factor" ], "offsets": [ [ 262, 330 ] ], "normalized": [] }, { "id": "684", "type": "protein_molecule", "text": [ "polyomavirus enhancer binding-protein 2" ], "offsets": [ [ 262, 301 ] ], "normalized": [] }, { "id": "685", "type": "protein_molecule", "text": [ "PEBP2" ], "offsets": [ [ 303, 308 ] ], "normalized": [] }, { "id": "686", "type": "(AND protein_subunit protein_subunit)", "text": [ "alpha and beta subunits" ], "offsets": [ [ 350, 373 ] ], "normalized": [] }, { "id": "687", "type": "", "text": [ "alpha" ], "offsets": [ [ 350, 355 ] ], "normalized": [] }, { "id": "688", "type": "", "text": [ "beta" ], "offsets": [ [ 360, 364 ] ], "normalized": [] }, { "id": "689", "type": "", "text": [ "subunits" ], "offsets": [ [ 365, 373 ] ], "normalized": [] }, { "id": "690", "type": "DNA_domain_or_region", "text": [ "alpha A" ], "offsets": [ [ 405, 412 ] ], "normalized": [] }, { "id": "691", "type": "DNA_domain_or_region", "text": [ "alpha B" ], "offsets": [ [ 417, 424 ] ], "normalized": [] }, { "id": "692", "type": "protein_subunit", "text": [ "alpha subunit" ], "offsets": [ [ 439, 452 ] ], "normalized": [] }, { "id": "693", "type": "DNA_domain_or_region", "text": [ "alpha B" ], "offsets": [ [ 454, 461 ] ], "normalized": [] }, { "id": "694", "type": "DNA_family_or_group", "text": [ "mouse homologue" ], "offsets": [ [ 469, 484 ] ], "normalized": [] }, { "id": "695", "type": "DNA_domain_or_region", "text": [ "human AML1 gene" ], "offsets": [ [ 488, 503 ] ], "normalized": [] }, { "id": "696", "type": "(AND other_artificial_source other_artificial_source)", "text": [ "t(8;21) and t(3;21) myeloid leukemias" ], "offsets": [ [ 535, 572 ] ], "normalized": [] }, { "id": "697", "type": "", "text": [ "t(8;21)" ], "offsets": [ [ 535, 542 ] ], "normalized": [] }, { "id": "698", "type": "", "text": [ "t(3;21)" ], "offsets": [ [ 547, 554 ] ], "normalized": [] }, { "id": "699", "type": "", "text": [ "myeloid leukemias" ], "offsets": [ [ 555, 572 ] ], "normalized": [] }, { "id": "700", "type": "protein_subunit", "text": [ "alpha A1" ], "offsets": [ [ 586, 594 ] ], "normalized": [] }, { "id": "701", "type": "protein_family_or_group", "text": [ "alpha A-gene product" ], "offsets": [ [ 599, 619 ] ], "normalized": [] }, { "id": "702", "type": "DNA_domain_or_region", "text": [ "alpha A" ], "offsets": [ [ 586, 593 ] ], "normalized": [] }, { "id": "703", "type": "protein_subunit", "text": [ "alpha B1" ], "offsets": [ [ 625, 633 ] ], "normalized": [] }, { "id": "704", "type": "protein_subunit", "text": [ "alpha B2" ], "offsets": [ [ 638, 646 ] ], "normalized": [] }, { "id": "705", "type": "protein_family_or_group", "text": [ "alpha B-encoded isomers" ], "offsets": [ [ 652, 675 ] ], "normalized": [] }, { "id": "706", "type": "DNA_domain_or_region", "text": [ "alpha B" ], "offsets": [ [ 625, 632 ] ], "normalized": [] }, { "id": "707", "type": "protein_subunit", "text": [ "alpha B" ], "offsets": [ [ 625, 632 ] ], "normalized": [] }, { "id": "708", "type": "DNA_domain_or_region", "text": [ "GM-CSF promoter" ], "offsets": [ [ 702, 717 ] ], "normalized": [] }, { "id": "709", "type": "protein_molecule", "text": [ "PEBP2 alpha A1" ], "offsets": [ [ 719, 733 ] ], "normalized": [] }, { "id": "710", "type": "protein_molecule", "text": [ "PEBP2" ], "offsets": [ [ 719, 724 ] ], "normalized": [] }, { "id": "711", "type": "protein_subunit", "text": [ "alpha A1" ], "offsets": [ [ 725, 733 ] ], "normalized": [] }, { "id": "712", "type": "protein_subunit", "text": [ "alpha B1" ], "offsets": [ [ 735, 743 ] ], "normalized": [] }, { "id": "713", "type": "protein_family_or_group", "text": [ "alpha B2 proteins" ], "offsets": [ [ 749, 766 ] ], "normalized": [] }, { "id": "714", "type": "DNA_domain_or_region", "text": [ "PEBP2 site" ], "offsets": [ [ 777, 787 ] ], "normalized": [] }, { "id": "715", "type": "protein_molecule", "text": [ "PEBP2" ], "offsets": [ [ 777, 782 ] ], "normalized": [] }, { "id": "716", "type": "DNA_domain_or_region", "text": [ "mouse GM-CSF promoter" ], "offsets": [ [ 799, 820 ] ], "normalized": [] }, { "id": "717", "type": "protein_molecule", "text": [ "GM-CSF" ], "offsets": [ [ 805, 811 ] ], "normalized": [] }, { "id": "718", "type": "protein_molecule", "text": [ "PEBP2 alpha A1" ], "offsets": [ [ 822, 836 ] ], "normalized": [] }, { "id": "719", "type": "protein_molecule", "text": [ "PEBP2" ], "offsets": [ [ 822, 827 ] ], "normalized": [] }, { "id": "720", "type": "protein_subunit", "text": [ "alpha A1" ], "offsets": [ [ 828, 836 ] ], "normalized": [] }, { "id": "721", "type": "protein_subunit", "text": [ "alpha B1" ], "offsets": [ [ 841, 849 ] ], "normalized": [] }, { "id": "722", "type": "DNA_molecule", "text": [ "GM-CSF promoter-driven reporter plasmid" ], "offsets": [ [ 881, 920 ] ], "normalized": [] }, { "id": "723", "type": "protein_molecule", "text": [ "GM-CSF" ], "offsets": [ [ 881, 887 ] ], "normalized": [] }, { "id": "724", "type": "(AND cell_line cell_line)", "text": [ "unstimulated and 12-O-tetradecanoylphorbol 13-acetate/phytohemagglutinin-stimulated human Jurkat T cells" ], "offsets": [ [ 924, 1028 ] ], "normalized": [] }, { "id": "725", "type": "", "text": [ "unstimulated" ], "offsets": [ [ 924, 936 ] ], "normalized": [] }, { "id": "726", "type": "", "text": [ "12-O-tetradecanoylphorbol 13-acetate/phytohemagglutinin-stimulated" ], "offsets": [ [ 941, 1007 ] ], "normalized": [] }, { "id": "727", "type": "", "text": [ "human Jurkat T cells" ], "offsets": [ [ 1008, 1028 ] ], "normalized": [] }, { "id": "728", "type": "other_name", "text": [ "promoter activity" ], "offsets": [ [ 1047, 1064 ] ], "normalized": [] }, { "id": "729", "type": "protein_subunit", "text": [ "alpha B2" ], "offsets": [ [ 1083, 1091 ] ], "normalized": [] }, { "id": "730", "type": "protein_subunit", "text": [ "alpha B1" ], "offsets": [ [ 1109, 1117 ] ], "normalized": [] }, { "id": "731", "type": "protein_subunit", "text": [ "alpha B2" ], "offsets": [ [ 1122, 1130 ] ], "normalized": [] }, { "id": "732", "type": "other_name", "text": [ "promoter activity" ], "offsets": [ [ 1147, 1164 ] ], "normalized": [] }, { "id": "733", "type": "other_name", "text": [ "alpha B1/alpha B2 ratio" ], "offsets": [ [ 1192, 1215 ] ], "normalized": [] }, { "id": "734", "type": "protein_subunit", "text": [ "alpha B1" ], "offsets": [ [ 1192, 1200 ] ], "normalized": [] }, { "id": "735", "type": "protein_subunit", "text": [ "/alpha B2" ], "offsets": [ [ 1200, 1209 ] ], "normalized": [] }, { "id": "736", "type": "cell_component", "text": [ "Jurkat cell extract" ], "offsets": [ [ 1217, 1236 ] ], "normalized": [] }, { "id": "737", "type": "protein_family_or_group", "text": [ "PEBP2 site-binding protein" ], "offsets": [ [ 1247, 1273 ] ], "normalized": [] }, { "id": "738", "type": "protein_molecule", "text": [ "PEBP2" ], "offsets": [ [ 1247, 1252 ] ], "normalized": [] }, { "id": "739", "type": "protein_family_or_group", "text": [ "antimouse alpha A1 antibodies" ], "offsets": [ [ 1301, 1330 ] ], "normalized": [] }, { "id": "740", "type": "protein_subunit", "text": [ "alpha A1" ], "offsets": [ [ 1311, 1319 ] ], "normalized": [] }, { "id": "741", "type": "other_name", "text": [ "Northern blot analysis" ], "offsets": [ [ 1332, 1354 ] ], "normalized": [] }, { "id": "742", "type": "protein_molecule", "text": [ "PEBP2 alpha A" ], "offsets": [ [ 1389, 1402 ] ], "normalized": [] }, { "id": "743", "type": "protein_molecule", "text": [ "PEBP2" ], "offsets": [ [ 1389, 1394 ] ], "normalized": [] }, { "id": "744", "type": "DNA_domain_or_region", "text": [ "alpha B" ], "offsets": [ [ 1404, 1411 ] ], "normalized": [] }, { "id": "745", "type": "protein_subunit", "text": [ "alpha B" ], "offsets": [ [ 1404, 1411 ] ], "normalized": [] }, { "id": "746", "type": "DNA_domain_or_region", "text": [ "AML1" ], "offsets": [ [ 1413, 1417 ] ], "normalized": [] }, { "id": "747", "type": "DNA_domain_or_region", "text": [ "beta genes" ], "offsets": [ [ 1424, 1434 ] ], "normalized": [] }, { "id": "748", "type": "cell_line", "text": [ "Jurkat cells" ], "offsets": [ [ 1438, 1450 ] ], "normalized": [] }, { "id": "749", "type": "protein_molecule", "text": [ "PEBP2" ], "offsets": [ [ 1523, 1528 ] ], "normalized": [] }, { "id": "750", "type": "other_name", "text": [ "GM-CSF promoter activity" ], "offsets": [ [ 1536, 1560 ] ], "normalized": [] }, { "id": "751", "type": "protein_molecule", "text": [ "GM-CSF" ], "offsets": [ [ 1536, 1542 ] ], "normalized": [] }, { "id": "752", "type": "other_name", "text": [ "promoter activity" ], "offsets": [ [ 1543, 1560 ] ], "normalized": [] }, { "id": "753", "type": "protein_family_or_group", "text": [ "PEBP2 isoforms" ], "offsets": [ [ 1643, 1657 ] ], "normalized": [] }, { "id": "754", "type": "protein_molecule", "text": [ "PEBP2" ], "offsets": [ [ 1643, 1648 ] ], "normalized": [] }, { "id": "755", "type": "other_name", "text": [ "promoter activity" ], "offsets": [ [ 1690, 1707 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "757", "type": "title", "text": [ "IFN-gamma priming of monocytes enhances LPS-induced TNF production by augmenting both transcription and MRNA stability." ], "offsets": [ [ 0, 119 ] ] }, { "id": "758", "type": "abstract", "text": [ "The induction of cytokine expression in monocytes/macrophages by bacterial endotoxin or lipopolysaccharide is a critical, highly regulated host defence response. The augmentation of LPS responses by interferon gamma (IFN-gamma), referred to as priming, is well established. However, the mechanism(s) by which priming occurs is poorly defined. Using tumour necrosis factor (TNF) induction as a model, experiments were designed to analyse in detail the priming effect on the LPS response in human monocytes. Priming by IFN-gamma was primarily manifested at the level of TNF mRNA accumulation. IFN-gamma pre-treatment affected the magnitude rather than the sensitivity of the LPS response. Priming occurred after several hours of treatment, and the primed state was induced by either IFN-gamma or GM-CSF, but not M-CSF. Primed monocytes transcribed TNF mRNA at a higher rate than freshly isolated monocytes upon activation with LPS. The increased transcriptional rate correlated with a marked increase in nuclear factor-kappa B activity in these cells as determined by electrophoretic mobility shift assay using a consensus NF-kappa B oligonucleotide. An additional significant finding was than TNF mRNA induced in primed cells was much more stable than in unprimed cells (T1/2 increased 6-8-fold). Consistent with the increased mRNA stability, the duration of mRNA accumulation was longer following LPS stimulation in primed monocytes, in addition to being of greater magnitude. Finally, primed and unprimed cells possessed a differential sensitivity to the kinase inhibitor H-89. H-89 substantially suppressed LPS-induced TNF mRNA accumulation in unprimed cells, but had no effect on primed monocytes following LPS stimulation. (ABSTRACT TRUNCATED AT 250 WORDS)" ], "offsets": [ [ 120, 1880 ] ] } ]

[ { "id": "759", "type": "protein_molecule", "text": [ "IFN-gamma" ], "offsets": [ [ 0, 9 ] ], "normalized": [] }, { "id": "760", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 21, 30 ] ], "normalized": [] }, { "id": "761", "type": "other_name", "text": [ "LPS-induced TNF production" ], "offsets": [ [ 40, 66 ] ], "normalized": [] }, { "id": "762", "type": "lipid", "text": [ "LPS" ], "offsets": [ [ 40, 43 ] ], "normalized": [] }, { "id": "763", "type": "protein_family_or_group", "text": [ "TNF" ], "offsets": [ [ 52, 55 ] ], "normalized": [] }, { "id": "764", "type": "other_name", "text": [ "transcription" ], "offsets": [ [ 86, 99 ] ], "normalized": [] }, { "id": "765", "type": "other_name", "text": [ "MRNA stability" ], "offsets": [ [ 104, 118 ] ], "normalized": [] }, { "id": "766", "type": "other_name", "text": [ "cytokine expression" ], "offsets": [ [ 137, 156 ] ], "normalized": [] }, { "id": "767", "type": "protein_family_or_group", "text": [ "cytokine" ], "offsets": [ [ 137, 145 ] ], "normalized": [] }, { "id": "768", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 160, 169 ] ], "normalized": [] }, { "id": "769", "type": "cell_type", "text": [ "macrophages" ], "offsets": [ [ 170, 181 ] ], "normalized": [] }, { "id": "770", "type": "protein_family_or_group", "text": [ "bacterial endotoxin" ], "offsets": [ [ 185, 204 ] ], "normalized": [] }, { "id": "771", "type": "lipid", "text": [ "lipopolysaccharide" ], "offsets": [ [ 208, 226 ] ], "normalized": [] }, { "id": "772", "type": "other_name", "text": [ "host defence response" ], "offsets": [ [ 259, 280 ] ], "normalized": [] }, { "id": "773", "type": "lipid", "text": [ "LPS" ], "offsets": [ [ 302, 305 ] ], "normalized": [] }, { "id": "774", "type": "protein_molecule", "text": [ "interferon gamma" ], "offsets": [ [ 319, 335 ] ], "normalized": [] }, { "id": "775", "type": "protein_molecule", "text": [ "IFN-gamma" ], "offsets": [ [ 337, 346 ] ], "normalized": [] }, { "id": "776", "type": "other_name", "text": [ "tumour necrosis factor (TNF) induction" ], "offsets": [ [ 469, 507 ] ], "normalized": [] }, { "id": "777", "type": "protein_family_or_group", "text": [ "tumour necrosis factor" ], "offsets": [ [ 469, 491 ] ], "normalized": [] }, { "id": "778", "type": "protein_family_or_group", "text": [ "TNF" ], "offsets": [ [ 493, 496 ] ], "normalized": [] }, { "id": "779", "type": "other_name", "text": [ "priming effect" ], "offsets": [ [ 571, 585 ] ], "normalized": [] }, { "id": "780", "type": "lipid", "text": [ "LPS" ], "offsets": [ [ 593, 596 ] ], "normalized": [] }, { "id": "781", "type": "cell_type", "text": [ "human monocytes" ], "offsets": [ [ 609, 624 ] ], "normalized": [] }, { "id": "782", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 615, 624 ] ], "normalized": [] }, { "id": "783", "type": "protein_molecule", "text": [ "IFN-gamma" ], "offsets": [ [ 637, 646 ] ], "normalized": [] }, { "id": "784", "type": "other_name", "text": [ "TNF mRNA accumulation" ], "offsets": [ [ 688, 709 ] ], "normalized": [] }, { "id": "785", "type": "RNA_family_or_group", "text": [ "TNF mRNA" ], "offsets": [ [ 688, 696 ] ], "normalized": [] }, { "id": "786", "type": "protein_family_or_group", "text": [ "TNF" ], "offsets": [ [ 688, 691 ] ], "normalized": [] }, { "id": "787", "type": "other_name", "text": [ "IFN-gamma pre-treatment" ], "offsets": [ [ 711, 734 ] ], "normalized": [] }, { "id": "788", "type": "protein_molecule", "text": [ "IFN-gamma" ], "offsets": [ [ 711, 720 ] ], "normalized": [] }, { "id": "789", "type": "other_name", "text": [ "LPS response" ], "offsets": [ [ 793, 805 ] ], "normalized": [] }, { "id": "790", "type": "lipid", "text": [ "LPS" ], "offsets": [ [ 793, 796 ] ], "normalized": [] }, { "id": "791", "type": "other_name", "text": [ "treatment" ], "offsets": [ [ 847, 856 ] ], "normalized": [] }, { "id": "792", "type": "other_name", "text": [ "primed state" ], "offsets": [ [ 866, 878 ] ], "normalized": [] }, { "id": "793", "type": "protein_molecule", "text": [ "IFN-gamma" ], "offsets": [ [ 901, 910 ] ], "normalized": [] }, { "id": "794", "type": "protein_molecule", "text": [ "GM-CSF" ], "offsets": [ [ 914, 920 ] ], "normalized": [] }, { "id": "795", "type": "protein_molecule", "text": [ "M-CSF" ], "offsets": [ [ 915, 920 ] ], "normalized": [] }, { "id": "796", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 944, 953 ] ], "normalized": [] }, { "id": "797", "type": "RNA_family_or_group", "text": [ "TNF mRNA" ], "offsets": [ [ 966, 974 ] ], "normalized": [] }, { "id": "798", "type": "protein_family_or_group", "text": [ "TNF" ], "offsets": [ [ 966, 969 ] ], "normalized": [] }, { "id": "799", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 1014, 1023 ] ], "normalized": [] }, { "id": "800", "type": "lipid", "text": [ "LPS" ], "offsets": [ [ 1045, 1048 ] ], "normalized": [] }, { "id": "801", "type": "other_name", "text": [ "transcriptional rate" ], "offsets": [ [ 1064, 1084 ] ], "normalized": [] }, { "id": "802", "type": "other_name", "text": [ "nuclear factor-kappa B activity" ], "offsets": [ [ 1122, 1153 ] ], "normalized": [] }, { "id": "803", "type": "protein_molecule", "text": [ "nuclear factor-kappa B" ], "offsets": [ [ 1122, 1144 ] ], "normalized": [] }, { "id": "804", "type": "other_name", "text": [ "electrophoretic mobility shift assay" ], "offsets": [ [ 1186, 1222 ] ], "normalized": [] }, { "id": "805", "type": "DNA_molecule", "text": [ "consensus NF-kappa B oligonucleotide" ], "offsets": [ [ 1231, 1267 ] ], "normalized": [] }, { "id": "806", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 1241, 1251 ] ], "normalized": [] }, { "id": "807", "type": "RNA_family_or_group", "text": [ "TNF mRNA" ], "offsets": [ [ 1312, 1320 ] ], "normalized": [] }, { "id": "808", "type": "protein_family_or_group", "text": [ "TNF" ], "offsets": [ [ 1312, 1315 ] ], "normalized": [] }, { "id": "809", "type": "cell_line", "text": [ "primed cells" ], "offsets": [ [ 1332, 1344 ] ], "normalized": [] }, { "id": "810", "type": "cell_line", "text": [ "unprimed cells" ], "offsets": [ [ 1374, 1388 ] ], "normalized": [] }, { "id": "811", "type": "other_name", "text": [ "mRNA stability" ], "offsets": [ [ 1446, 1460 ] ], "normalized": [] }, { "id": "812", "type": "RNA_family_or_group", "text": [ "mRNA" ], "offsets": [ [ 1446, 1450 ] ], "normalized": [] }, { "id": "813", "type": "other_name", "text": [ "mRNA accumulation" ], "offsets": [ [ 1478, 1495 ] ], "normalized": [] }, { "id": "814", "type": "RNA_family_or_group", "text": [ "mRNA" ], "offsets": [ [ 1478, 1482 ] ], "normalized": [] }, { "id": "815", "type": "lipid", "text": [ "LPS" ], "offsets": [ [ 1517, 1520 ] ], "normalized": [] }, { "id": "816", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 1543, 1552 ] ], "normalized": [] }, { "id": "817", "type": "other_organic_compound", "text": [ "kinase inhibitor H-89" ], "offsets": [ [ 1676, 1697 ] ], "normalized": [] }, { "id": "818", "type": "other_organic_compound", "text": [ "H-89" ], "offsets": [ [ 1699, 1703 ] ], "normalized": [] }, { "id": "819", "type": "other_name", "text": [ "LPS-induced TNF mRNA accumulation" ], "offsets": [ [ 1729, 1762 ] ], "normalized": [] }, { "id": "820", "type": "lipid", "text": [ "LPS" ], "offsets": [ [ 1729, 1732 ] ], "normalized": [] }, { "id": "821", "type": "RNA_family_or_group", "text": [ "TNF mRNA" ], "offsets": [ [ 1741, 1749 ] ], "normalized": [] }, { "id": "822", "type": "protein_family_or_group", "text": [ "TNF" ], "offsets": [ [ 1741, 1744 ] ], "normalized": [] }, { "id": "823", "type": "cell_line", "text": [ "unprimed cells" ], "offsets": [ [ 1766, 1780 ] ], "normalized": [] }, { "id": "824", "type": "cell_line", "text": [ "primed monocytes" ], "offsets": [ [ 1803, 1819 ] ], "normalized": [] }, { "id": "825", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 1810, 1819 ] ], "normalized": [] }, { "id": "826", "type": "other_name", "text": [ "LPS stimulation" ], "offsets": [ [ 1830, 1845 ] ], "normalized": [] }, { "id": "827", "type": "lipid", "text": [ "LPS" ], "offsets": [ [ 1830, 1833 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "829", "type": "title", "text": [ "A Myc-associated zinc finger protein binding site is one of four important functional regions in the CD4 promoter." ], "offsets": [ [ 0, 114 ] ] }, { "id": "830", "type": "abstract", "text": [ "The CD4 promoter plays an important role in the developmental control of CD4 transcription. In this report, we show that the minimal CD4 promoter has four factor binding sites, each of which is required for full function. Using biochemical and mutagenesis analyses, we determined that multiple nuclear factors bind to these independent sites. We determined that an initiator-like sequence present at the cap site and an Ets consensus sequence are required for full promoter function. We also demonstrate that the Myc-associated zinc finger protein (MAZ) appears to be the predominant factor binding to one of these sites. This last site closely resembles the ME1a1 G3AG4AG3 motif previously shown to be a critical element in the P2 promoter of the c-myc gene. We therefore believe that the MAZ transcription factor is also likely to play an important role in the control of developmental expression of the CD4 gene." ], "offsets": [ [ 115, 1030 ] ] } ]

[ { "id": "831", "type": "DNA_domain_or_region", "text": [ "Myc-associated zinc finger protein binding site" ], "offsets": [ [ 2, 49 ] ], "normalized": [] }, { "id": "832", "type": "protein_family_or_group", "text": [ "Myc-associated zinc finger protein" ], "offsets": [ [ 2, 36 ] ], "normalized": [] }, { "id": "833", "type": "DNA_domain_or_region", "text": [ "functional regions" ], "offsets": [ [ 75, 93 ] ], "normalized": [] }, { "id": "834", "type": "DNA_domain_or_region", "text": [ "CD4 promoter" ], "offsets": [ [ 101, 113 ] ], "normalized": [] }, { "id": "835", "type": "protein_molecule", "text": [ "CD4" ], "offsets": [ [ 101, 104 ] ], "normalized": [] }, { "id": "836", "type": "DNA_domain_or_region", "text": [ "CD4 promoter" ], "offsets": [ [ 119, 131 ] ], "normalized": [] }, { "id": "837", "type": "protein_molecule", "text": [ "CD4" ], "offsets": [ [ 119, 122 ] ], "normalized": [] }, { "id": "838", "type": "other_name", "text": [ "developmental control" ], "offsets": [ [ 163, 184 ] ], "normalized": [] }, { "id": "839", "type": "other_name", "text": [ "CD4 transcription" ], "offsets": [ [ 188, 205 ] ], "normalized": [] }, { "id": "840", "type": "protein_molecule", "text": [ "CD4" ], "offsets": [ [ 188, 191 ] ], "normalized": [] }, { "id": "841", "type": "DNA_domain_or_region", "text": [ "CD4 promoter" ], "offsets": [ [ 248, 260 ] ], "normalized": [] }, { "id": "842", "type": "protein_molecule", "text": [ "CD4" ], "offsets": [ [ 248, 251 ] ], "normalized": [] }, { "id": "843", "type": "DNA_domain_or_region", "text": [ "factor binding sites" ], "offsets": [ [ 270, 290 ] ], "normalized": [] }, { "id": "844", "type": "(AND other_name other_name)", "text": [ "biochemical and mutagenesis analyses" ], "offsets": [ [ 343, 379 ] ], "normalized": [] }, { "id": "845", "type": "", "text": [ "biochemical" ], "offsets": [ [ 343, 354 ] ], "normalized": [] }, { "id": "846", "type": "", "text": [ "mutagenesis" ], "offsets": [ [ 359, 370 ] ], "normalized": [] }, { "id": "847", "type": "", "text": [ "analyses" ], "offsets": [ [ 371, 379 ] ], "normalized": [] }, { "id": "848", "type": "protein_family_or_group", "text": [ "nuclear factors" ], "offsets": [ [ 409, 424 ] ], "normalized": [] }, { "id": "849", "type": "DNA_domain_or_region", "text": [ "initiator-like sequence" ], "offsets": [ [ 480, 503 ] ], "normalized": [] }, { "id": "850", "type": "DNA_domain_or_region", "text": [ "cap site" ], "offsets": [ [ 519, 527 ] ], "normalized": [] }, { "id": "851", "type": "DNA_domain_or_region", "text": [ "Ets consensus sequence" ], "offsets": [ [ 535, 557 ] ], "normalized": [] }, { "id": "852", "type": "other_name", "text": [ "promoter function" ], "offsets": [ [ 580, 597 ] ], "normalized": [] }, { "id": "853", "type": "DNA_domain_or_region", "text": [ "promoter" ], "offsets": [ [ 580, 588 ] ], "normalized": [] }, { "id": "854", "type": "protein_molecule", "text": [ "Myc-associated zinc finger protein" ], "offsets": [ [ 628, 662 ] ], "normalized": [] }, { "id": "855", "type": "protein_substructure", "text": [ "zinc finger" ], "offsets": [ [ 643, 654 ] ], "normalized": [] }, { "id": "856", "type": "protein_molecule", "text": [ "MAZ" ], "offsets": [ [ 664, 667 ] ], "normalized": [] }, { "id": "857", "type": "protein_family_or_group", "text": [ "predominant factor" ], "offsets": [ [ 687, 705 ] ], "normalized": [] }, { "id": "858", "type": "DNA_domain_or_region", "text": [ "ME1a1 G3AG4AG3 motif" ], "offsets": [ [ 774, 794 ] ], "normalized": [] }, { "id": "859", "type": "DNA_domain_or_region", "text": [ "P2 promoter" ], "offsets": [ [ 844, 855 ] ], "normalized": [] }, { "id": "860", "type": "DNA_domain_or_region", "text": [ "c-myc gene" ], "offsets": [ [ 863, 873 ] ], "normalized": [] }, { "id": "861", "type": "protein_family_or_group", "text": [ "MAZ transcription factor" ], "offsets": [ [ 905, 929 ] ], "normalized": [] }, { "id": "862", "type": "protein_molecule", "text": [ "MAZ" ], "offsets": [ [ 905, 908 ] ], "normalized": [] }, { "id": "863", "type": "other_name", "text": [ "developmental expression" ], "offsets": [ [ 989, 1013 ] ], "normalized": [] }, { "id": "864", "type": "DNA_domain_or_region", "text": [ "CD4 gene" ], "offsets": [ [ 1021, 1029 ] ], "normalized": [] }, { "id": "865", "type": "protein_molecule", "text": [ "CD4" ], "offsets": [ [ 1021, 1024 ] ], "normalized": [] } ]

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[ { "id": "867", "type": "title", "text": [ "Erythropoietin stimulates transcription of the TAL1/SCL gene and phosphorylation of its protein products." ], "offsets": [ [ 0, 105 ] ] }, { "id": "868", "type": "abstract", "text": [ "Activation of the TAL1 (or SCL) gene, originally identified through its involvement by a recurrent chromosomal translocation, is the most frequent molecular lesion recognized in T-cell acute lymphoblastic leukemia. The protein products of this gene contain the basic-helix-loop-helix motif characteristic of a large family of transcription factors that bind to the canonical DNA sequence CANNTG as protein heterodimers. TAL1 expression by erythroid cells in vivo and in chemical-induced erythroleukemia cell lines in vivo suggested the gene might regulate aspects of erythroid differentiation. Since the terminal events of erythropoiesis are controlled by the glycoprotein hormone erythropoietin (Epo), we investigated whether the expression or activity of the TAL1 gene and its protein products were affected by Epo in splenic erythroblasts from mice infected with an anemia-inducing strain of Friend virus (FVA cells). Epo elicited a rapid, dose-related increase in TAL1 mRNA by increasing transcription of the gene and stabilizing one of its mRNAs. An Epo-inducible TAL1 DNA binding activity was identified in FVA cell nuclear extracts that subsequently decayed despite accumulating mRNA and protein. Induction of DNA binding activity was associated temporally with Epo-induced phosphorylation of nuclear TAL1 protein. These results indicate that Epo acts at both transcriptional and posttranscriptional levels on the TAL1 locus in Friend virus-induced erythroblasts and establish a link between Epo signaling mechanisms and a member of a family of transcription factors involved in the differentiation of diverse cell lineages." ], "offsets": [ [ 106, 1737 ] ] } ]

[ { "id": "869", "type": "protein_molecule", "text": [ "Erythropoietin" ], "offsets": [ [ 0, 14 ] ], "normalized": [] }, { "id": "870", "type": "DNA_domain_or_region", "text": [ "TAL1/SCL gene" ], "offsets": [ [ 47, 60 ] ], "normalized": [] }, { "id": "871", "type": "other_name", "text": [ "phosphorylation" ], "offsets": [ [ 65, 80 ] ], "normalized": [] }, { "id": "872", "type": "protein_domain_or_region", "text": [ "protein products" ], "offsets": [ [ 88, 104 ] ], "normalized": [] }, { "id": "873", "type": "DNA_domain_or_region", "text": [ "TAL1 (or SCL) gene" ], "offsets": [ [ 124, 142 ] ], "normalized": [] }, { "id": "874", "type": "other_name", "text": [ "recurrent chromosomal translocation" ], "offsets": [ [ 195, 230 ] ], "normalized": [] }, { "id": "875", "type": "DNA_N/A", "text": [ "molecular lesion" ], "offsets": [ [ 253, 269 ] ], "normalized": [] }, { "id": "876", "type": "other_name", "text": [ "T-cell acute lymphoblastic leukemia" ], "offsets": [ [ 284, 319 ] ], "normalized": [] }, { "id": "877", "type": "protein_family_or_group", "text": [ "protein products" ], "offsets": [ [ 325, 341 ] ], "normalized": [] }, { "id": "878", "type": "protein_family_or_group", "text": [ "basic-helix-loop-helix motif" ], "offsets": [ [ 367, 395 ] ], "normalized": [] }, { "id": "879", "type": "protein_family_or_group", "text": [ "transcription factors" ], "offsets": [ [ 432, 453 ] ], "normalized": [] }, { "id": "880", "type": "DNA_domain_or_region", "text": [ "canonical DNA sequence CANNTG" ], "offsets": [ [ 471, 500 ] ], "normalized": [] }, { "id": "881", "type": "protein_family_or_group", "text": [ "protein heterodimers" ], "offsets": [ [ 504, 524 ] ], "normalized": [] }, { "id": "882", "type": "other_name", "text": [ "TAL1 expression" ], "offsets": [ [ 526, 541 ] ], "normalized": [] }, { "id": "883", "type": "protein_molecule", "text": [ "TAL1" ], "offsets": [ [ 526, 530 ] ], "normalized": [] }, { "id": "884", "type": "cell_type", "text": [ "erythroid cells" ], "offsets": [ [ 545, 560 ] ], "normalized": [] }, { "id": "885", "type": "cell_line", "text": [ "chemical-induced erythroleukemia cell lines" ], "offsets": [ [ 576, 619 ] ], "normalized": [] }, { "id": "886", "type": "other_name", "text": [ "erythroid differentiation" ], "offsets": [ [ 673, 698 ] ], "normalized": [] }, { "id": "887", "type": "other_name", "text": [ "erythropoiesis" ], "offsets": [ [ 729, 743 ] ], "normalized": [] }, { "id": "888", "type": "protein_molecule", "text": [ "glycoprotein hormone erythropoietin" ], "offsets": [ [ 766, 801 ] ], "normalized": [] }, { "id": "889", "type": "protein_molecule", "text": [ "Epo" ], "offsets": [ [ 803, 806 ] ], "normalized": [] }, { "id": "890", "type": "DNA_domain_or_region", "text": [ "TAL1 gene" ], "offsets": [ [ 867, 876 ] ], "normalized": [] }, { "id": "891", "type": "protein_molecule", "text": [ "TAL1" ], "offsets": [ [ 867, 871 ] ], "normalized": [] }, { "id": "892", "type": "protein_family_or_group", "text": [ "protein products" ], "offsets": [ [ 885, 901 ] ], "normalized": [] }, { "id": "893", "type": "protein_molecule", "text": [ "Epo" ], "offsets": [ [ 919, 922 ] ], "normalized": [] }, { "id": "894", "type": "cell_type", "text": [ "splenic erythroblasts" ], "offsets": [ [ 926, 947 ] ], "normalized": [] }, { "id": "895", "type": "multi_cell", "text": [ "mice" ], "offsets": [ [ 953, 957 ] ], "normalized": [] }, { "id": "896", "type": "protein_molecule", "text": [ "Epo" ], "offsets": [ [ 1027, 1030 ] ], "normalized": [] }, { "id": "897", "type": "RNA_family_or_group", "text": [ "TAL1 mRNA" ], "offsets": [ [ 1074, 1083 ] ], "normalized": [] }, { "id": "898", "type": "protein_molecule", "text": [ "TAL1" ], "offsets": [ [ 1074, 1078 ] ], "normalized": [] }, { "id": "899", "type": "other_name", "text": [ "transcription" ], "offsets": [ [ 1098, 1111 ] ], "normalized": [] }, { "id": "900", "type": "RNA_family_or_group", "text": [ "mRNAs" ], "offsets": [ [ 1151, 1156 ] ], "normalized": [] }, { "id": "901", "type": "other_name", "text": [ "Epo-inducible TAL1 DNA binding activity" ], "offsets": [ [ 1161, 1200 ] ], "normalized": [] }, { "id": "902", "type": "protein_molecule", "text": [ "Epo" ], "offsets": [ [ 1161, 1164 ] ], "normalized": [] }, { "id": "903", "type": "protein_molecule", "text": [ "TAL1" ], "offsets": [ [ 1175, 1179 ] ], "normalized": [] }, { "id": "904", "type": "cell_component", "text": [ "FVA cell nuclear extracts" ], "offsets": [ [ 1219, 1244 ] ], "normalized": [] }, { "id": "905", "type": "RNA_family_or_group", "text": [ "mRNA" ], "offsets": [ [ 1292, 1296 ] ], "normalized": [] }, { "id": "906", "type": "protein_N/A", "text": [ "protein" ], "offsets": [ [ 1301, 1308 ] ], "normalized": [] }, { "id": "907", "type": "other_name", "text": [ "DNA binding activity" ], "offsets": [ [ 1323, 1343 ] ], "normalized": [] }, { "id": "908", "type": "other_name", "text": [ "Epo-induced phosphorylation" ], "offsets": [ [ 1375, 1402 ] ], "normalized": [] }, { "id": "909", "type": "protein_molecule", "text": [ "Epo" ], "offsets": [ [ 1375, 1378 ] ], "normalized": [] }, { "id": "910", "type": "other_name", "text": [ "phosphorylation" ], "offsets": [ [ 1387, 1402 ] ], "normalized": [] }, { "id": "911", "type": "protein_molecule", "text": [ "nuclear TAL1 protein" ], "offsets": [ [ 1406, 1426 ] ], "normalized": [] }, { "id": "912", "type": "protein_molecule", "text": [ "TAL1" ], "offsets": [ [ 1414, 1418 ] ], "normalized": [] }, { "id": "913", "type": "protein_molecule", "text": [ "Epo" ], "offsets": [ [ 1456, 1459 ] ], "normalized": [] }, { "id": "914", "type": "(AND other_name other_name)", "text": [ "transcriptional and posttranscriptional levels" ], "offsets": [ [ 1473, 1519 ] ], "normalized": [] }, { "id": "915", "type": "", "text": [ "transcriptional" ], "offsets": [ [ 1473, 1488 ] ], "normalized": [] }, { "id": "916", "type": "", "text": [ "posttranscriptional" ], "offsets": [ [ 1493, 1512 ] ], "normalized": [] }, { "id": "917", "type": "", "text": [ "levels" ], "offsets": [ [ 1513, 1519 ] ], "normalized": [] }, { "id": "918", "type": "protein_molecule", "text": [ "TAL1" ], "offsets": [ [ 1527, 1531 ] ], "normalized": [] }, { "id": "919", "type": "cell_line", "text": [ "Friend virus-induced erythroblasts" ], "offsets": [ [ 1541, 1575 ] ], "normalized": [] }, { "id": "920", "type": "virus", "text": [ "Friend virus" ], "offsets": [ [ 1541, 1553 ] ], "normalized": [] }, { "id": "921", "type": "other_name", "text": [ "Epo signaling mechanisms" ], "offsets": [ [ 1605, 1629 ] ], "normalized": [] }, { "id": "922", "type": "protein_molecule", "text": [ "Epo" ], "offsets": [ [ 1605, 1608 ] ], "normalized": [] }, { "id": "923", "type": "protein_family_or_group", "text": [ "transcription factors" ], "offsets": [ [ 1658, 1679 ] ], "normalized": [] }, { "id": "924", "type": "cell_type", "text": [ "diverse cell lineages" ], "offsets": [ [ 1715, 1736 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "926", "type": "title", "text": [ "Nonradioactive quantification of glucocorticoid receptor expression during differentiation of human monocytic cells (U937)." ], "offsets": [ [ 0, 123 ] ] }, { "id": "927", "type": "abstract", "text": [ "We describe a method for relative quantification of specific mRNA using a nonradioactive assay based on DNA strand competition between identical sequences of biotin- and fluorescein-labeled amplicon (probe) and unlabeled amplicon (target) during hybridization. As the target quantity increased, that of the double-labeled probe decreased in accordance with the mass action law. This technique was successfully applied to evaluate differences in glucocorticoid receptor expression in U937 cells before and after the addition of potent differentiation inducers: 12-O-tetradecanoylphorbol 13-acetate (TPA) and a combination of all-trans retinoic acid (RA) and 1,25-dihydroxyvitamin D2 (VD). We observed that TPA treatment was associated with an increase in specific binding of [3H]dexamethasone and up-regulation of GR mRNA while no enhanced GR expression was perceived with RA/VD treatment." ], "offsets": [ [ 124, 1012 ] ] } ]

[ { "id": "928", "type": "other_name", "text": [ "Nonradioactive quantification" ], "offsets": [ [ 0, 29 ] ], "normalized": [] }, { "id": "929", "type": "other_name", "text": [ "glucocorticoid receptor expression" ], "offsets": [ [ 33, 67 ] ], "normalized": [] }, { "id": "930", "type": "protein_domain_or_region", "text": [ "glucocorticoid receptor" ], "offsets": [ [ 33, 56 ] ], "normalized": [] }, { "id": "931", "type": "cell_type", "text": [ "monocytic cells" ], "offsets": [ [ 100, 115 ] ], "normalized": [] }, { "id": "932", "type": "cell_line", "text": [ "U937" ], "offsets": [ [ 117, 121 ] ], "normalized": [] }, { "id": "933", "type": "RNA_family_or_group", "text": [ "mRNA" ], "offsets": [ [ 185, 189 ] ], "normalized": [] }, { "id": "934", "type": "other_name", "text": [ "nonradioactive assay" ], "offsets": [ [ 198, 218 ] ], "normalized": [] }, { "id": "935", "type": "other_name", "text": [ "DNA strand competition" ], "offsets": [ [ 228, 250 ] ], "normalized": [] }, { "id": "936", "type": "other_organic_compound", "text": [ "biotin- and fluorescein-labeled amplicon" ], "offsets": [ [ 282, 322 ] ], "normalized": [] }, { "id": "937", "type": "other_organic_compound", "text": [ "unlabeled amplicon" ], "offsets": [ [ 335, 353 ] ], "normalized": [] }, { "id": "938", "type": "other_name", "text": [ "hybridization" ], "offsets": [ [ 370, 383 ] ], "normalized": [] }, { "id": "939", "type": "other_organic_compound", "text": [ "double-labeled probe" ], "offsets": [ [ 431, 451 ] ], "normalized": [] }, { "id": "940", "type": "other_name", "text": [ "glucocorticoid receptor expression" ], "offsets": [ [ 569, 603 ] ], "normalized": [] }, { "id": "941", "type": "protein_domain_or_region", "text": [ "glucocorticoid receptor" ], "offsets": [ [ 569, 592 ] ], "normalized": [] }, { "id": "942", "type": "cell_line", "text": [ "U937 cells" ], "offsets": [ [ 607, 617 ] ], "normalized": [] }, { "id": "943", "type": "other_name", "text": [ "differentiation inducers" ], "offsets": [ [ 658, 682 ] ], "normalized": [] }, { "id": "944", "type": "other_organic_compound", "text": [ "12-O-tetradecanoylphorbol 13-acetate" ], "offsets": [ [ 684, 720 ] ], "normalized": [] }, { "id": "945", "type": "other_organic_compound", "text": [ "TPA" ], "offsets": [ [ 722, 725 ] ], "normalized": [] }, { "id": "946", "type": "other_organic_compound", "text": [ "all-trans retinoic acid" ], "offsets": [ [ 748, 771 ] ], "normalized": [] }, { "id": "947", "type": "other_organic_compound", "text": [ "RA" ], "offsets": [ [ 773, 775 ] ], "normalized": [] }, { "id": "948", "type": "other_organic_compound", "text": [ "1,25-dihydroxyvitamin D2" ], "offsets": [ [ 781, 805 ] ], "normalized": [] }, { "id": "949", "type": "other_organic_compound", "text": [ "VD" ], "offsets": [ [ 807, 809 ] ], "normalized": [] }, { "id": "950", "type": "other_organic_compound", "text": [ "TPA" ], "offsets": [ [ 829, 832 ] ], "normalized": [] }, { "id": "951", "type": "lipid", "text": [ "[3H]dexamethasone" ], "offsets": [ [ 898, 915 ] ], "normalized": [] }, { "id": "952", "type": "RNA_family_or_group", "text": [ "GR mRNA" ], "offsets": [ [ 937, 944 ] ], "normalized": [] }, { "id": "953", "type": "protein_family_or_group", "text": [ "GR" ], "offsets": [ [ 937, 939 ] ], "normalized": [] }, { "id": "954", "type": "other_name", "text": [ "GR expression" ], "offsets": [ [ 963, 976 ] ], "normalized": [] }, { "id": "955", "type": "protein_family_or_group", "text": [ "GR" ], "offsets": [ [ 963, 965 ] ], "normalized": [] }, { "id": "956", "type": "other_name", "text": [ "RA/VD treatment" ], "offsets": [ [ 996, 1011 ] ], "normalized": [] } ]

[]

[]

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[ { "id": "958", "type": "title", "text": [ "Induction of Sp1 phosphorylation and NF-kappa B-independent HIV promoter domain activity in T lymphocytes stimulated by okadaic acid." ], "offsets": [ [ 0, 133 ] ] }, { "id": "959", "type": "abstract", "text": [ "In contrast to the purely enhancer-dependent effect of cytokines such as TNF on the activity of the HIV regulatory region (LTR), we observed that okadaic acid (OKA) activates HIV transcription through both the enhancer, responding to the factor NF-kappa B, and the promoter domain of the LTR. The inducibility of HIV LTR-driven luciferase expression constructs in lymphoblastoid cells stimulated by OKA depended on both functional Sp1 binding elements and the ability of the TATA box to bind the protein TBP. In both transformed and normal lymphocytes, OKA stimulation induced intense phosphorylation of the constitutively expressed Sp1 protein in the nucleus, a property of OKA not shared by TNF, phorbol ester, or PHA and interleukin 2. Responsiveness of LTR constructs deleted of kappa B elements to HIV Tat expression was increased upon OKA but not TNF stimulation. Our results suggest that SP1 phosphorylation induced by OKA, a selective inhibitor of the serine-threonine phosphatase PP2A, facilitates the formation of a transcription complex involving general transcription factors, HIV Tat, and Sp1 proteins. The formation of this complex would increase, independently of an in synergy with NF-kappa B, the low basal activity of the HIV LTR observed in normal T lymphocytes." ], "offsets": [ [ 134, 1415 ] ] } ]

[ { "id": "960", "type": "other_name", "text": [ "Sp1 phosphorylation" ], "offsets": [ [ 13, 32 ] ], "normalized": [] }, { "id": "961", "type": "protein_molecule", "text": [ "Sp1" ], "offsets": [ [ 13, 16 ] ], "normalized": [] }, { "id": "962", "type": "other_name", "text": [ "phosphorylation" ], "offsets": [ [ 17, 32 ] ], "normalized": [] }, { "id": "963", "type": "other_name", "text": [ "NF-kappa B-independent HIV promoter domain activity" ], "offsets": [ [ 37, 88 ] ], "normalized": [] }, { "id": "964", "type": "DNA_domain_or_region", "text": [ "NF-kappa B-independent HIV promoter" ], "offsets": [ [ 37, 72 ] ], "normalized": [] }, { "id": "965", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 37, 47 ] ], "normalized": [] }, { "id": "966", "type": "virus", "text": [ "HIV" ], "offsets": [ [ 60, 63 ] ], "normalized": [] }, { "id": "967", "type": "cell_type", "text": [ "T lymphocytes" ], "offsets": [ [ 92, 105 ] ], "normalized": [] }, { "id": "968", "type": "other_organic_compound", "text": [ "okadaic acid" ], "offsets": [ [ 120, 132 ] ], "normalized": [] }, { "id": "969", "type": "other_name", "text": [ "enhancer-dependent effect" ], "offsets": [ [ 160, 185 ] ], "normalized": [] }, { "id": "970", "type": "protein_family_or_group", "text": [ "cytokines" ], "offsets": [ [ 189, 198 ] ], "normalized": [] }, { "id": "971", "type": "protein_family_or_group", "text": [ "TNF" ], "offsets": [ [ 207, 210 ] ], "normalized": [] }, { "id": "972", "type": "DNA_domain_or_region", "text": [ "HIV regulatory region" ], "offsets": [ [ 234, 255 ] ], "normalized": [] }, { "id": "973", "type": "virus", "text": [ "HIV" ], "offsets": [ [ 234, 237 ] ], "normalized": [] }, { "id": "974", "type": "DNA_domain_or_region", "text": [ "LTR" ], "offsets": [ [ 257, 260 ] ], "normalized": [] }, { "id": "975", "type": "other_organic_compound", "text": [ "okadaic acid" ], "offsets": [ [ 280, 292 ] ], "normalized": [] }, { "id": "976", "type": "other_organic_compound", "text": [ "OKA" ], "offsets": [ [ 294, 297 ] ], "normalized": [] }, { "id": "977", "type": "other_name", "text": [ "HIV transcription" ], "offsets": [ [ 309, 326 ] ], "normalized": [] }, { "id": "978", "type": "virus", "text": [ "HIV" ], "offsets": [ [ 309, 312 ] ], "normalized": [] }, { "id": "979", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 379, 389 ] ], "normalized": [] }, { "id": "980", "type": "DNA_domain_or_region", "text": [ "promoter domain" ], "offsets": [ [ 399, 414 ] ], "normalized": [] }, { "id": "981", "type": "DNA_domain_or_region", "text": [ "LTR" ], "offsets": [ [ 422, 425 ] ], "normalized": [] }, { "id": "982", "type": "DNA_family_or_group", "text": [ "HIV LTR-driven luciferase expression constructs" ], "offsets": [ [ 447, 494 ] ], "normalized": [] }, { "id": "983", "type": "DNA_domain_or_region", "text": [ "HIV LTR" ], "offsets": [ [ 447, 454 ] ], "normalized": [] }, { "id": "984", "type": "virus", "text": [ "HIV" ], "offsets": [ [ 447, 450 ] ], "normalized": [] }, { "id": "985", "type": "protein_molecule", "text": [ "luciferase" ], "offsets": [ [ 462, 472 ] ], "normalized": [] }, { "id": "986", "type": "cell_type", "text": [ "lymphoblastoid cells" ], "offsets": [ [ 498, 518 ] ], "normalized": [] }, { "id": "987", "type": "other_organic_compound", "text": [ "OKA" ], "offsets": [ [ 533, 536 ] ], "normalized": [] }, { "id": "988", "type": "DNA_domain_or_region", "text": [ "functional Sp1 binding elements" ], "offsets": [ [ 554, 585 ] ], "normalized": [] }, { "id": "989", "type": "protein_molecule", "text": [ "Sp1" ], "offsets": [ [ 565, 568 ] ], "normalized": [] }, { "id": "990", "type": "DNA_domain_or_region", "text": [ "TATA box" ], "offsets": [ [ 609, 617 ] ], "normalized": [] }, { "id": "991", "type": "protein_molecule", "text": [ "TBP" ], "offsets": [ [ 638, 641 ] ], "normalized": [] }, { "id": "992", "type": "(AND cell_type cell_type)", "text": [ "transformed and normal lymphocytes" ], "offsets": [ [ 651, 685 ] ], "normalized": [] }, { "id": "993", "type": "", "text": [ "transformed" ], "offsets": [ [ 651, 662 ] ], "normalized": [] }, { "id": "994", "type": "", "text": [ "normal" ], "offsets": [ [ 667, 673 ] ], "normalized": [] }, { "id": "995", "type": "", "text": [ "lymphocytes" ], "offsets": [ [ 674, 685 ] ], "normalized": [] }, { "id": "996", "type": "other_name", "text": [ "OKA stimulation" ], "offsets": [ [ 687, 702 ] ], "normalized": [] }, { "id": "997", "type": "other_organic_compound", "text": [ "OKA" ], "offsets": [ [ 687, 690 ] ], "normalized": [] }, { "id": "998", "type": "other_name", "text": [ "phosphorylation" ], "offsets": [ [ 719, 734 ] ], "normalized": [] }, { "id": "999", "type": "protein_molecule", "text": [ "Sp1 protein" ], "offsets": [ [ 767, 778 ] ], "normalized": [] }, { "id": "1000", "type": "protein_molecule", "text": [ "Sp1" ], "offsets": [ [ 767, 770 ] ], "normalized": [] }, { "id": "1001", "type": "cell_component", "text": [ "nucleus" ], "offsets": [ [ 786, 793 ] ], "normalized": [] }, { "id": "1002", "type": "other_organic_compound", "text": [ "OKA" ], "offsets": [ [ 809, 812 ] ], "normalized": [] }, { "id": "1003", "type": "protein_family_or_group", "text": [ "TNF" ], "offsets": [ [ 827, 830 ] ], "normalized": [] }, { "id": "1004", "type": "other_organic_compound", "text": [ "phorbol ester" ], "offsets": [ [ 832, 845 ] ], "normalized": [] }, { "id": "1005", "type": "protein_molecule", "text": [ "PHA" ], "offsets": [ [ 850, 853 ] ], "normalized": [] }, { "id": "1006", "type": "protein_molecule", "text": [ "interleukin 2" ], "offsets": [ [ 858, 871 ] ], "normalized": [] }, { "id": "1007", "type": "DNA_family_or_group", "text": [ "LTR constructs" ], "offsets": [ [ 891, 905 ] ], "normalized": [] }, { "id": "1008", "type": "DNA_family_or_group", "text": [ "kappa B elements" ], "offsets": [ [ 917, 933 ] ], "normalized": [] }, { "id": "1009", "type": "other_name", "text": [ "HIV Tat expression" ], "offsets": [ [ 937, 955 ] ], "normalized": [] }, { "id": "1010", "type": "protein_molecule", "text": [ "HIV Tat" ], "offsets": [ [ 937, 944 ] ], "normalized": [] }, { "id": "1011", "type": "virus", "text": [ "HIV" ], "offsets": [ [ 937, 940 ] ], "normalized": [] }, { "id": "1012", "type": "(BUT_NOT other_name other_name)", "text": [ "OKA but not TNF stimulation" ], "offsets": [ [ 975, 1002 ] ], "normalized": [] }, { "id": "1013", "type": "other_organic_compound", "text": [ "OKA" ], "offsets": [ [ 975, 978 ] ], "normalized": [] }, { "id": "1014", "type": "", "text": [ "OKA" ], "offsets": [ [ 975, 978 ] ], "normalized": [] }, { "id": "1015", "type": "protein_family_or_group", "text": [ "TNF" ], "offsets": [ [ 987, 990 ] ], "normalized": [] }, { "id": "1016", "type": "", "text": [ "TNF" ], "offsets": [ [ 987, 990 ] ], "normalized": [] }, { "id": "1017", "type": "", "text": [ "stimulation" ], "offsets": [ [ 991, 1002 ] ], "normalized": [] }, { "id": "1018", "type": "protein_molecule", "text": [ "SP1" ], "offsets": [ [ 1029, 1032 ] ], "normalized": [] }, { "id": "1019", "type": "other_name", "text": [ "phosphorylation" ], "offsets": [ [ 1033, 1048 ] ], "normalized": [] }, { "id": "1020", "type": "other_organic_compound", "text": [ "OKA" ], "offsets": [ [ 1060, 1063 ] ], "normalized": [] }, { "id": "1021", "type": "protein_family_or_group", "text": [ "serine-threonine phosphatase" ], "offsets": [ [ 1094, 1122 ] ], "normalized": [] }, { "id": "1022", "type": "protein_molecule", "text": [ "PP2A" ], "offsets": [ [ 1123, 1127 ] ], "normalized": [] }, { "id": "1023", "type": "protein_complex", "text": [ "transcription complex" ], "offsets": [ [ 1160, 1181 ] ], "normalized": [] }, { "id": "1024", "type": "protein_family_or_group", "text": [ "transcription factors" ], "offsets": [ [ 1200, 1221 ] ], "normalized": [] }, { "id": "1025", "type": "protein_molecule", "text": [ "HIV Tat" ], "offsets": [ [ 1223, 1230 ] ], "normalized": [] }, { "id": "1026", "type": "virus", "text": [ "HIV" ], "offsets": [ [ 1223, 1226 ] ], "normalized": [] }, { "id": "1027", "type": "protein_family_or_group", "text": [ "Sp1 proteins" ], "offsets": [ [ 1236, 1248 ] ], "normalized": [] }, { "id": "1028", "type": "protein_molecule", "text": [ "Sp1" ], "offsets": [ [ 1236, 1239 ] ], "normalized": [] }, { "id": "1029", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 1332, 1342 ] ], "normalized": [] }, { "id": "1030", "type": "other_name", "text": [ "basal activity" ], "offsets": [ [ 1352, 1366 ] ], "normalized": [] }, { "id": "1031", "type": "DNA_domain_or_region", "text": [ "HIV LTR" ], "offsets": [ [ 1374, 1381 ] ], "normalized": [] }, { "id": "1032", "type": "virus", "text": [ "HIV" ], "offsets": [ [ 1374, 1377 ] ], "normalized": [] }, { "id": "1033", "type": "cell_type", "text": [ "normal T lymphocytes" ], "offsets": [ [ 1394, 1414 ] ], "normalized": [] }, { "id": "1034", "type": "cell_type", "text": [ "T lymphocytes" ], "offsets": [ [ 1401, 1414 ] ], "normalized": [] } ]

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[]

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[ { "id": "1036", "type": "title", "text": [ "The role of shared receptor motifs and common Stat proteins in the generation of cytokine pleiotropy and redundancy by IL-2, IL-4, IL-7, IL-13, and IL-15." ], "offsets": [ [ 0, 154 ] ] }, { "id": "1037", "type": "abstract", "text": [ "To understand the molecular bases for cytokine redundancy and pleiotropy, we have compared the Stat proteins activated in peripheral blood lymphocytes (PBLs) by cytokines with shared and distinct actions. Interleukin-2 (IL-2) rapidly activated Stat5 in fresh PBL, and Stat3 and Stat5 in preactivated PBL. IL-7 and IL-15 induced the same complexes as IL-2, a feature explained by the existence of similar tyrosine-phosphorylated motifs in the cytoplasmic domains of IL-2R beta and IL-7R that can serve as docking sites for Stat proteins. IL-13 Induced the same complexes as IL-4, a finding explained by our studies implicating IL-4R as a shared component of the receptors. These studies demonstrate that a single cytokine can activate different combinations of Stat proteins under different physiological conditions, and also indicate two mechanisms by which distinct cytokines can activate the same Stat protein." ], "offsets": [ [ 155, 1067 ] ] } ]

[ { "id": "1038", "type": "protein_substructure", "text": [ "shared receptor motifs" ], "offsets": [ [ 12, 34 ] ], "normalized": [] }, { "id": "1039", "type": "protein_family_or_group", "text": [ "common Stat proteins" ], "offsets": [ [ 39, 59 ] ], "normalized": [] }, { "id": "1040", "type": "other_name", "text": [ "cytokine pleiotropy" ], "offsets": [ [ 81, 100 ] ], "normalized": [] }, { "id": "1041", "type": "protein_family_or_group", "text": [ "cytokine" ], "offsets": [ [ 81, 89 ] ], "normalized": [] }, { "id": "1042", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 119, 123 ] ], "normalized": [] }, { "id": "1043", "type": "protein_molecule", "text": [ "IL-4" ], "offsets": [ [ 125, 129 ] ], "normalized": [] }, { "id": "1044", "type": "protein_molecule", "text": [ "IL-7" ], "offsets": [ [ 131, 135 ] ], "normalized": [] }, { "id": "1045", "type": "protein_molecule", "text": [ "IL-13" ], "offsets": [ [ 137, 142 ] ], "normalized": [] }, { "id": "1046", "type": "protein_molecule", "text": [ "IL-15" ], "offsets": [ [ 148, 153 ] ], "normalized": [] }, { "id": "1047", "type": "(AND other_name other_name)", "text": [ "cytokine redundancy and pleiotropy" ], "offsets": [ [ 193, 227 ] ], "normalized": [] }, { "id": "1048", "type": "", "text": [ "cytokine" ], "offsets": [ [ 193, 201 ] ], "normalized": [] }, { "id": "1049", "type": "", "text": [ "redundancy" ], "offsets": [ [ 202, 212 ] ], "normalized": [] }, { "id": "1050", "type": "", "text": [ "pleiotropy" ], "offsets": [ [ 217, 227 ] ], "normalized": [] }, { "id": "1051", "type": "protein_family_or_group", "text": [ "Stat proteins" ], "offsets": [ [ 250, 263 ] ], "normalized": [] }, { "id": "1052", "type": "cell_type", "text": [ "peripheral blood lymphocytes" ], "offsets": [ [ 277, 305 ] ], "normalized": [] }, { "id": "1053", "type": "cell_type", "text": [ "PBLs" ], "offsets": [ [ 307, 311 ] ], "normalized": [] }, { "id": "1054", "type": "protein_family_or_group", "text": [ "cytokines" ], "offsets": [ [ 316, 325 ] ], "normalized": [] }, { "id": "1055", "type": "protein_molecule", "text": [ "Interleukin-2" ], "offsets": [ [ 360, 373 ] ], "normalized": [] }, { "id": "1056", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 375, 379 ] ], "normalized": [] }, { "id": "1057", "type": "protein_molecule", "text": [ "Stat5" ], "offsets": [ [ 399, 404 ] ], "normalized": [] }, { "id": "1058", "type": "cell_type", "text": [ "PBL" ], "offsets": [ [ 414, 417 ] ], "normalized": [] }, { "id": "1059", "type": "protein_molecule", "text": [ "Stat3" ], "offsets": [ [ 423, 428 ] ], "normalized": [] }, { "id": "1060", "type": "protein_molecule", "text": [ "Stat5" ], "offsets": [ [ 433, 438 ] ], "normalized": [] }, { "id": "1061", "type": "cell_type", "text": [ "preactivated PBL" ], "offsets": [ [ 442, 458 ] ], "normalized": [] }, { "id": "1062", "type": "protein_molecule", "text": [ "IL-7" ], "offsets": [ [ 460, 464 ] ], "normalized": [] }, { "id": "1063", "type": "protein_molecule", "text": [ "IL-15" ], "offsets": [ [ 469, 474 ] ], "normalized": [] }, { "id": "1064", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 505, 509 ] ], "normalized": [] }, { "id": "1065", "type": "protein_substructure", "text": [ "tyrosine-phosphorylated motifs" ], "offsets": [ [ 559, 589 ] ], "normalized": [] }, { "id": "1066", "type": "amino_acid_monomer", "text": [ "tyrosine" ], "offsets": [ [ 559, 567 ] ], "normalized": [] }, { "id": "1067", "type": "protein_domain_or_region", "text": [ "cytoplasmic domains" ], "offsets": [ [ 597, 616 ] ], "normalized": [] }, { "id": "1068", "type": "protein_molecule", "text": [ "IL-2R beta" ], "offsets": [ [ 620, 630 ] ], "normalized": [] }, { "id": "1069", "type": "protein_molecule", "text": [ "IL-7R" ], "offsets": [ [ 635, 640 ] ], "normalized": [] }, { "id": "1070", "type": "protein_family_or_group", "text": [ "Stat proteins" ], "offsets": [ [ 677, 690 ] ], "normalized": [] }, { "id": "1071", "type": "protein_molecule", "text": [ "IL-13" ], "offsets": [ [ 692, 697 ] ], "normalized": [] }, { "id": "1072", "type": "protein_molecule", "text": [ "IL-4" ], "offsets": [ [ 728, 732 ] ], "normalized": [] }, { "id": "1073", "type": "protein_molecule", "text": [ "IL-4R" ], "offsets": [ [ 781, 786 ] ], "normalized": [] }, { "id": "1074", "type": "protein_family_or_group", "text": [ "receptors" ], "offsets": [ [ 816, 825 ] ], "normalized": [] }, { "id": "1075", "type": "protein_family_or_group", "text": [ "cytokine" ], "offsets": [ [ 867, 875 ] ], "normalized": [] }, { "id": "1076", "type": "protein_family_or_group", "text": [ "Stat proteins" ], "offsets": [ [ 915, 928 ] ], "normalized": [] }, { "id": "1077", "type": "other_name", "text": [ "physiological conditions" ], "offsets": [ [ 945, 969 ] ], "normalized": [] }, { "id": "1078", "type": "protein_family_or_group", "text": [ "cytokines" ], "offsets": [ [ 1022, 1031 ] ], "normalized": [] }, { "id": "1079", "type": "protein_family_or_group", "text": [ "Stat protein" ], "offsets": [ [ 915, 927 ] ], "normalized": [] } ]

[]

[]

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[ { "id": "1081", "type": "title", "text": [ "Control of I kappa B-alpha proteolysis by site-specific, signal-induced phosphorylation." ], "offsets": [ [ 0, 88 ] ] }, { "id": "1082", "type": "abstract", "text": [ "I kappa B-alpha inhibits transcription factor NF-kappa B by retaining it in the cytoplasm. Various stimuli, typically those associated with stress or pathogens, rapidly inactivate I kappa B-alpha. This liberates NF-kappa B to translocate to the nucleus and initiate transcription of genes important for the defense of the organism. Activation of NF-kappa B correlates with phosphorylation of I kappa B-alpha and requires the proteolysis of this inhibitor. When either serine-32 or serine-36 of I kappa B-alpha was mutated, the protein did not undergo signal-induced phosphorylation or degradation, and NF-kappa B could not be activated. These results suggest that phosphorylation at one or both of these residues is critical for activation of NF-kappa B." ], "offsets": [ [ 89, 843 ] ] } ]

[ { "id": "1083", "type": "other_name", "text": [ "I kappa B-alpha proteolysis" ], "offsets": [ [ 11, 38 ] ], "normalized": [] }, { "id": "1084", "type": "protein_molecule", "text": [ "I kappa B-alpha" ], "offsets": [ [ 11, 26 ] ], "normalized": [] }, { "id": "1085", "type": "other_name", "text": [ "phosphorylation" ], "offsets": [ [ 72, 87 ] ], "normalized": [] }, { "id": "1086", "type": "protein_molecule", "text": [ "I kappa B-alpha" ], "offsets": [ [ 89, 104 ] ], "normalized": [] }, { "id": "1087", "type": "protein_family_or_group", "text": [ "transcription factor" ], "offsets": [ [ 114, 134 ] ], "normalized": [] }, { "id": "1088", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 135, 145 ] ], "normalized": [] }, { "id": "1089", "type": "cell_component", "text": [ "cytoplasm" ], "offsets": [ [ 169, 178 ] ], "normalized": [] }, { "id": "1090", "type": "protein_molecule", "text": [ "I kappa B-alpha" ], "offsets": [ [ 269, 284 ] ], "normalized": [] }, { "id": "1091", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 301, 311 ] ], "normalized": [] }, { "id": "1092", "type": "cell_component", "text": [ "nucleus" ], "offsets": [ [ 334, 341 ] ], "normalized": [] }, { "id": "1093", "type": "other_name", "text": [ "transcription" ], "offsets": [ [ 355, 368 ] ], "normalized": [] }, { "id": "1094", "type": "DNA_family_or_group", "text": [ "genes" ], "offsets": [ [ 372, 377 ] ], "normalized": [] }, { "id": "1095", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 435, 445 ] ], "normalized": [] }, { "id": "1096", "type": "other_name", "text": [ "phosphorylation" ], "offsets": [ [ 462, 477 ] ], "normalized": [] }, { "id": "1097", "type": "protein_molecule", "text": [ "I kappa B-alpha" ], "offsets": [ [ 481, 496 ] ], "normalized": [] }, { "id": "1098", "type": "other_name", "text": [ "proteolysis" ], "offsets": [ [ 514, 525 ] ], "normalized": [] }, { "id": "1099", "type": "amino_acid_monomer", "text": [ "serine-32" ], "offsets": [ [ 557, 566 ] ], "normalized": [] }, { "id": "1100", "type": "amino_acid_monomer", "text": [ "serine-36" ], "offsets": [ [ 570, 579 ] ], "normalized": [] }, { "id": "1101", "type": "protein_molecule", "text": [ "I kappa B-alpha" ], "offsets": [ [ 583, 598 ] ], "normalized": [] }, { "id": "1102", "type": "other_name", "text": [ "signal-induced phosphorylation" ], "offsets": [ [ 640, 670 ] ], "normalized": [] }, { "id": "1103", "type": "other_name", "text": [ "phosphorylation" ], "offsets": [ [ 655, 670 ] ], "normalized": [] }, { "id": "1104", "type": "other_name", "text": [ "degradation" ], "offsets": [ [ 674, 685 ] ], "normalized": [] }, { "id": "1105", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 691, 701 ] ], "normalized": [] }, { "id": "1106", "type": "other_name", "text": [ "phosphorylation" ], "offsets": [ [ 753, 768 ] ], "normalized": [] }, { "id": "1107", "type": "amino_acid_monomer", "text": [ "residues" ], "offsets": [ [ 793, 801 ] ], "normalized": [] }, { "id": "1108", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 832, 842 ] ], "normalized": [] } ]

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[ { "id": "1110", "type": "title", "text": [ "Regulation of transcription of the human erythropoietin receptor gene by proteins binding to GATA-1 and Sp1 motifs." ], "offsets": [ [ 0, 115 ] ] }, { "id": "1111", "type": "abstract", "text": [ "Erythropoietin (Epo), the primary regulator of the production of erythroid cells, acts by binding to a cell surface receptor (EpoR) on erythroid progenitors. We used deletion analysis and transfection assays with reporter gene constructs to examine the transcription control elements in the 5' flanking region of the human EpoR gene. In erythroid cells most of the transcription activity was contained in a 150 bp promoter fragment with binding sites for transcription factors AP2, Sp1 and the erythroid-specific GATA-1. The 150 bp hEpoR promoter exhibited high and low activity in erythroid OCIM1 and K562 cells, respectively, reflecting the high and low levels of constitutive hEpoR expression. The GATA-1 and Sp1 binding sites in this promoter lacking a TATA sequence were necessary for a high level of transcription activation. Protein-DNA binding studies suggested that Sp1 and two other CCGCCC binding proteins from erythroid and non-erythroid cells could bind to the Sp1 binding motif. By increasing GATA-1 levels via co-transfection, we were able to transactivate the hEpoR promoter in K562 cells and non-erythroid cells, but not in the highly active OCIM1 cells, although GATA-1 mRNA levels were comparable in OCIM1 and K562. Interestingly, when we mutated the Sp1 site, resulting in a marked decrease in hEpoR promoter activity, we could restore transactivation by increasing GATA-1 levels in OCIM1 cells. These data suggest that while GATA-1 can transactivate the EpoR promoter, the level of hEpoR gene expression does not depend on GATA-1 alone. Rather, hEpoR transcription activity depends on coordination between Sp1 and GATA-1 with other cell-specific factors, including possibly other Sp1-like binding proteins, to provide high level, tissue-specific expression." ], "offsets": [ [ 116, 1894 ] ] } ]

[ { "id": "1112", "type": "other_name", "text": [ "transcription" ], "offsets": [ [ 14, 27 ] ], "normalized": [] }, { "id": "1113", "type": "DNA_domain_or_region", "text": [ "human erythropoietin receptor gene" ], "offsets": [ [ 35, 69 ] ], "normalized": [] }, { "id": "1114", "type": "DNA_domain_or_region", "text": [ "GATA-1 and Sp1 motifs" ], "offsets": [ [ 93, 114 ] ], "normalized": [] }, { "id": "1115", "type": "DNA_domain_or_region", "text": [ "GATA-1" ], "offsets": [ [ 93, 99 ] ], "normalized": [] }, { "id": "1116", "type": "DNA_domain_or_region", "text": [ "Sp1 motifs" ], "offsets": [ [ 104, 114 ] ], "normalized": [] }, { "id": "1117", "type": "protein_molecule", "text": [ "Erythropoietin" ], "offsets": [ [ 116, 130 ] ], "normalized": [] }, { "id": "1118", "type": "protein_molecule", "text": [ "Epo" ], "offsets": [ [ 132, 135 ] ], "normalized": [] }, { "id": "1119", "type": "cell_type", "text": [ "erythroid cells" ], "offsets": [ [ 181, 196 ] ], "normalized": [] }, { "id": "1120", "type": "protein_family_or_group", "text": [ "cell surface receptor" ], "offsets": [ [ 219, 240 ] ], "normalized": [] }, { "id": "1121", "type": "protein_molecule", "text": [ "EpoR" ], "offsets": [ [ 242, 246 ] ], "normalized": [] }, { "id": "1122", "type": "cell_type", "text": [ "erythroid progenitors" ], "offsets": [ [ 251, 272 ] ], "normalized": [] }, { "id": "1123", "type": "other_name", "text": [ "deletion analysis" ], "offsets": [ [ 282, 299 ] ], "normalized": [] }, { "id": "1124", "type": "other_name", "text": [ "transfection assays" ], "offsets": [ [ 304, 323 ] ], "normalized": [] }, { "id": "1125", "type": "DNA_family_or_group", "text": [ "reporter gene constructs" ], "offsets": [ [ 329, 353 ] ], "normalized": [] }, { "id": "1126", "type": "DNA_domain_or_region", "text": [ "transcription control elements" ], "offsets": [ [ 369, 399 ] ], "normalized": [] }, { "id": "1127", "type": "DNA_domain_or_region", "text": [ "5' flanking region" ], "offsets": [ [ 407, 425 ] ], "normalized": [] }, { "id": "1128", "type": "DNA_domain_or_region", "text": [ "human EpoR gene" ], "offsets": [ [ 433, 448 ] ], "normalized": [] }, { "id": "1129", "type": "protein_molecule", "text": [ "EpoR" ], "offsets": [ [ 439, 443 ] ], "normalized": [] }, { "id": "1130", "type": "cell_type", "text": [ "erythroid cells" ], "offsets": [ [ 453, 468 ] ], "normalized": [] }, { "id": "1131", "type": "other_name", "text": [ "transcription activity" ], "offsets": [ [ 481, 503 ] ], "normalized": [] }, { "id": "1132", "type": "DNA_domain_or_region", "text": [ "150 bp promoter" ], "offsets": [ [ 523, 538 ] ], "normalized": [] }, { "id": "1133", "type": "DNA_domain_or_region", "text": [ "binding sites" ], "offsets": [ [ 553, 566 ] ], "normalized": [] }, { "id": "1134", "type": "protein_family_or_group", "text": [ "transcription factors" ], "offsets": [ [ 571, 592 ] ], "normalized": [] }, { "id": "1135", "type": "protein_molecule", "text": [ "AP2" ], "offsets": [ [ 593, 596 ] ], "normalized": [] }, { "id": "1136", "type": "protein_molecule", "text": [ "Sp1" ], "offsets": [ [ 598, 601 ] ], "normalized": [] }, { "id": "1137", "type": "protein_molecule", "text": [ "erythroid-specific GATA-1" ], "offsets": [ [ 610, 635 ] ], "normalized": [] }, { "id": "1138", "type": "DNA_domain_or_region", "text": [ "150 bp hEpoR promoter" ], "offsets": [ [ 641, 662 ] ], "normalized": [] }, { "id": "1139", "type": "cell_line", "text": [ "OCIM1" ], "offsets": [ [ 708, 713 ] ], "normalized": [] }, { "id": "1140", "type": "cell_line", "text": [ "K562 cells" ], "offsets": [ [ 718, 728 ] ], "normalized": [] }, { "id": "1141", "type": "other_name", "text": [ "hEpoR expression" ], "offsets": [ [ 795, 811 ] ], "normalized": [] }, { "id": "1142", "type": "protein_molecule", "text": [ "hEpoR" ], "offsets": [ [ 648, 653 ] ], "normalized": [] }, { "id": "1143", "type": "(AND DNA_domain_or_region DNA_domain_or_region)", "text": [ "GATA-1 and Sp1 binding sites" ], "offsets": [ [ 817, 845 ] ], "normalized": [] }, { "id": "1144", "type": "", "text": [ "GATA-1" ], "offsets": [ [ 817, 823 ] ], "normalized": [] }, { "id": "1145", "type": "", "text": [ "Sp1" ], "offsets": [ [ 828, 831 ] ], "normalized": [] }, { "id": "1146", "type": "", "text": [ "binding sites" ], "offsets": [ [ 832, 845 ] ], "normalized": [] }, { "id": "1147", "type": "DNA_domain_or_region", "text": [ "TATA sequence" ], "offsets": [ [ 873, 886 ] ], "normalized": [] }, { "id": "1148", "type": "other_name", "text": [ "transcription activation" ], "offsets": [ [ 922, 946 ] ], "normalized": [] }, { "id": "1149", "type": "other_name", "text": [ "Protein-DNA binding studies" ], "offsets": [ [ 948, 975 ] ], "normalized": [] }, { "id": "1150", "type": "protein_molecule", "text": [ "Sp1" ], "offsets": [ [ 991, 994 ] ], "normalized": [] }, { "id": "1151", "type": "protein_family_or_group", "text": [ "CCGCCC binding proteins" ], "offsets": [ [ 1009, 1032 ] ], "normalized": [] }, { "id": "1152", "type": "(AND cell_type cell_type)", "text": [ "erythroid and non-erythroid cells" ], "offsets": [ [ 1038, 1071 ] ], "normalized": [] }, { "id": "1153", "type": "", "text": [ "erythroid" ], "offsets": [ [ 1038, 1047 ] ], "normalized": [] }, { "id": "1154", "type": "", "text": [ "non-erythroid" ], "offsets": [ [ 1052, 1065 ] ], "normalized": [] }, { "id": "1155", "type": "", "text": [ "cells" ], "offsets": [ [ 1066, 1071 ] ], "normalized": [] }, { "id": "1156", "type": "DNA_domain_or_region", "text": [ "Sp1 binding motif" ], "offsets": [ [ 1090, 1107 ] ], "normalized": [] }, { "id": "1157", "type": "protein_molecule", "text": [ "Sp1" ], "offsets": [ [ 1090, 1093 ] ], "normalized": [] }, { "id": "1158", "type": "other_name", "text": [ "GATA-1 levels" ], "offsets": [ [ 1123, 1136 ] ], "normalized": [] }, { "id": "1159", "type": "protein_molecule", "text": [ "GATA-1" ], "offsets": [ [ 1123, 1129 ] ], "normalized": [] }, { "id": "1160", "type": "other_name", "text": [ "co-transfection" ], "offsets": [ [ 1141, 1156 ] ], "normalized": [] }, { "id": "1161", "type": "DNA_domain_or_region", "text": [ "hEpoR promoter" ], "offsets": [ [ 1192, 1206 ] ], "normalized": [] }, { "id": "1162", "type": "cell_line", "text": [ "K562 cells" ], "offsets": [ [ 1210, 1220 ] ], "normalized": [] }, { "id": "1163", "type": "cell_type", "text": [ "non-erythroid cells" ], "offsets": [ [ 1225, 1244 ] ], "normalized": [] }, { "id": "1164", "type": "cell_type", "text": [ "OCIM1 cells" ], "offsets": [ [ 1275, 1286 ] ], "normalized": [] }, { "id": "1165", "type": "other_name", "text": [ "GATA-1 mRNA levels" ], "offsets": [ [ 1297, 1315 ] ], "normalized": [] }, { "id": "1166", "type": "RNA_molecule", "text": [ "GATA-1 mRNA" ], "offsets": [ [ 1297, 1308 ] ], "normalized": [] }, { "id": "1167", "type": "protein_molecule", "text": [ "GATA-1" ], "offsets": [ [ 1297, 1303 ] ], "normalized": [] }, { "id": "1168", "type": "cell_line", "text": [ "OCIM1" ], "offsets": [ [ 1275, 1280 ] ], "normalized": [] }, { "id": "1169", "type": "cell_line", "text": [ "K562" ], "offsets": [ [ 1210, 1214 ] ], "normalized": [] }, { "id": "1170", "type": "DNA_domain_or_region", "text": [ "Sp1 site" ], "offsets": [ [ 1386, 1394 ] ], "normalized": [] }, { "id": "1171", "type": "protein_molecule", "text": [ "Sp1" ], "offsets": [ [ 1386, 1389 ] ], "normalized": [] }, { "id": "1172", "type": "other_name", "text": [ "hEpoR promoter activity" ], "offsets": [ [ 1430, 1453 ] ], "normalized": [] }, { "id": "1173", "type": "DNA_domain_or_region", "text": [ "hEpoR promoter" ], "offsets": [ [ 1430, 1444 ] ], "normalized": [] }, { "id": "1174", "type": "other_name", "text": [ "transactivation" ], "offsets": [ [ 1472, 1487 ] ], "normalized": [] }, { "id": "1175", "type": "other_name", "text": [ "GATA-1 levels" ], "offsets": [ [ 1502, 1515 ] ], "normalized": [] }, { "id": "1176", "type": "protein_molecule", "text": [ "GATA-1" ], "offsets": [ [ 1502, 1508 ] ], "normalized": [] }, { "id": "1177", "type": "cell_type", "text": [ "OCIM1 cells" ], "offsets": [ [ 1519, 1530 ] ], "normalized": [] }, { "id": "1178", "type": "protein_molecule", "text": [ "GATA-1" ], "offsets": [ [ 1562, 1568 ] ], "normalized": [] }, { "id": "1179", "type": "DNA_domain_or_region", "text": [ "EpoR promoter" ], "offsets": [ [ 1591, 1604 ] ], "normalized": [] }, { "id": "1180", "type": "protein_molecule", "text": [ "EpoR" ], "offsets": [ [ 1591, 1595 ] ], "normalized": [] }, { "id": "1181", "type": "other_name", "text": [ "hEpoR gene expression" ], "offsets": [ [ 1619, 1640 ] ], "normalized": [] }, { "id": "1182", "type": "DNA_domain_or_region", "text": [ "hEpoR gene" ], "offsets": [ [ 1619, 1629 ] ], "normalized": [] }, { "id": "1183", "type": "protein_molecule", "text": [ "GATA-1" ], "offsets": [ [ 1660, 1666 ] ], "normalized": [] }, { "id": "1184", "type": "other_name", "text": [ "hEpoR transcription activity" ], "offsets": [ [ 1682, 1710 ] ], "normalized": [] }, { "id": "1185", "type": "protein_molecule", "text": [ "hEpoR" ], "offsets": [ [ 1682, 1687 ] ], "normalized": [] }, { "id": "1186", "type": "protein_molecule", "text": [ "Sp1" ], "offsets": [ [ 1743, 1746 ] ], "normalized": [] }, { "id": "1187", "type": "protein_molecule", "text": [ "GATA-1" ], "offsets": [ [ 1751, 1757 ] ], "normalized": [] }, { "id": "1188", "type": "protein_family_or_group", "text": [ "cell-specific factors" ], "offsets": [ [ 1769, 1790 ] ], "normalized": [] }, { "id": "1189", "type": "protein_family_or_group", "text": [ "Sp1-like binding proteins" ], "offsets": [ [ 1817, 1842 ] ], "normalized": [] }, { "id": "1190", "type": "protein_molecule", "text": [ "Sp1" ], "offsets": [ [ 1817, 1820 ] ], "normalized": [] }, { "id": "1191", "type": "other_name", "text": [ "tissue-specific expression" ], "offsets": [ [ 1867, 1893 ] ], "normalized": [] } ]

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[ { "id": "1193", "type": "title", "text": [ "Overexpression of DR-nm23, a protein encoded by a member of the nm23 gene family, inhibits granulocyte differentiation and induces apoptosis in 32Dc13 myeloid cells." ], "offsets": [ [ 0, 165 ] ] }, { "id": "1194", "type": "abstract", "text": [ "Chronic myelogenous leukemia evolves in two clinically distinct stages: a chronic and a blast crisis phase. The molecular changes associated with chronic phase to blast crisis transition are largely unknown. We have identified a cDNA clone, DR-nm23, differentially expressed in a blast-crisis cDNA library, which has approximately 70% sequence similarity to the putative metastatic suppressor genes, nm23-H1 and nm23-H2. The deduced amino acid sequence similarity to the proteins encoded by these two latter genes is approximately 65% and includes domains and amino acid residues (the leucine zipper-like and the RGD domain, a serine and a histidine residue in the NH2- and in the COOH-terminal portion of the protein, respectively) postulated to be important for nm23 function. DR-nm23 mRNA is preferentially expressed at early stages of myeloid differentiation of highly purified CD34+ cells. Its constitutive expression in the myeloid precursor 32Dc13 cell line, which is growth-factor dependent for both proliferation and differentiation, results in inhibition of granulocytic differentiation induced by granulocyte colony-stimulating factor and causes apoptotic cell death. These results are consistent with a role for DR-nm23 in normal hematopoiesis and raise the possibility that its overexpression contributes to differentiation arrest, a feature of blastic transformation in chronic myelogenous leukemia." ], "offsets": [ [ 166, 1579 ] ] } ]

[ { "id": "1195", "type": "protein_molecule", "text": [ "DR-nm23" ], "offsets": [ [ 18, 25 ] ], "normalized": [] }, { "id": "1196", "type": "DNA_family_or_group", "text": [ "nm23 gene family" ], "offsets": [ [ 64, 80 ] ], "normalized": [] }, { "id": "1197", "type": "other_name", "text": [ "granulocyte differentiation" ], "offsets": [ [ 91, 118 ] ], "normalized": [] }, { "id": "1198", "type": "cell_type", "text": [ "granulocyte" ], "offsets": [ [ 91, 102 ] ], "normalized": [] }, { "id": "1199", "type": "other_name", "text": [ "apoptosis" ], "offsets": [ [ 131, 140 ] ], "normalized": [] }, { "id": "1200", "type": "cell_line", "text": [ "32Dc13 myeloid cells" ], "offsets": [ [ 144, 164 ] ], "normalized": [] }, { "id": "1201", "type": "other_name", "text": [ "Chronic myelogenous leukemia" ], "offsets": [ [ 166, 194 ] ], "normalized": [] }, { "id": "1202", "type": "other_name", "text": [ "chronic" ], "offsets": [ [ 240, 247 ] ], "normalized": [] }, { "id": "1203", "type": "other_name", "text": [ "blast crisis phase" ], "offsets": [ [ 254, 272 ] ], "normalized": [] }, { "id": "1204", "type": "other_name", "text": [ "chronic phase" ], "offsets": [ [ 312, 325 ] ], "normalized": [] }, { "id": "1205", "type": "other_name", "text": [ "blast crisis" ], "offsets": [ [ 329, 341 ] ], "normalized": [] }, { "id": "1206", "type": "DNA_family_or_group", "text": [ "cDNA clone" ], "offsets": [ [ 395, 405 ] ], "normalized": [] }, { "id": "1207", "type": "protein_molecule", "text": [ "DR-nm23" ], "offsets": [ [ 407, 414 ] ], "normalized": [] }, { "id": "1208", "type": "DNA_family_or_group", "text": [ "blast-crisis cDNA library," ], "offsets": [ [ 446, 472 ] ], "normalized": [] }, { "id": "1209", "type": "DNA_family_or_group", "text": [ "putative metastatic suppressor genes" ], "offsets": [ [ 528, 564 ] ], "normalized": [] }, { "id": "1210", "type": "DNA_domain_or_region", "text": [ "nm23-H1" ], "offsets": [ [ 566, 573 ] ], "normalized": [] }, { "id": "1211", "type": "DNA_domain_or_region", "text": [ "nm23-H2" ], "offsets": [ [ 578, 585 ] ], "normalized": [] }, { "id": "1212", "type": "other_name", "text": [ "amino acid sequence similarity" ], "offsets": [ [ 599, 629 ] ], "normalized": [] }, { "id": "1213", "type": "protein_N/A", "text": [ "amino acid sequence" ], "offsets": [ [ 599, 618 ] ], "normalized": [] }, { "id": "1214", "type": "amino_acid_monomer", "text": [ "amino acid residues" ], "offsets": [ [ 726, 745 ] ], "normalized": [] }, { "id": "1215", "type": "protein_domain_or_region", "text": [ "leucine zipper-like" ], "offsets": [ [ 751, 770 ] ], "normalized": [] }, { "id": "1216", "type": "protein_domain_or_region", "text": [ "RGD domain" ], "offsets": [ [ 779, 789 ] ], "normalized": [] }, { "id": "1217", "type": "amino_acid_monomer", "text": [ "serine" ], "offsets": [ [ 793, 799 ] ], "normalized": [] }, { "id": "1218", "type": "amino_acid_monomer", "text": [ "histidine" ], "offsets": [ [ 806, 815 ] ], "normalized": [] }, { "id": "1219", "type": "protein_domain_or_region", "text": [ "NH2-" ], "offsets": [ [ 831, 835 ] ], "normalized": [] }, { "id": "1220", "type": "protein_domain_or_region", "text": [ "COOH-terminal portion" ], "offsets": [ [ 847, 868 ] ], "normalized": [] }, { "id": "1221", "type": "other_name", "text": [ "nm23 function" ], "offsets": [ [ 930, 943 ] ], "normalized": [] }, { "id": "1222", "type": "protein_molecule", "text": [ "nm23" ], "offsets": [ [ 930, 934 ] ], "normalized": [] }, { "id": "1223", "type": "RNA_molecule", "text": [ "DR-nm23 mRNA" ], "offsets": [ [ 945, 957 ] ], "normalized": [] }, { "id": "1224", "type": "protein_molecule", "text": [ "DR-nm23" ], "offsets": [ [ 945, 952 ] ], "normalized": [] }, { "id": "1225", "type": "other_name", "text": [ "myeloid differentiation" ], "offsets": [ [ 1005, 1028 ] ], "normalized": [] }, { "id": "1226", "type": "cell_line", "text": [ "highly purified CD34+ cells" ], "offsets": [ [ 1032, 1059 ] ], "normalized": [] }, { "id": "1227", "type": "cell_line", "text": [ "myeloid precursor 32Dc13 cell line" ], "offsets": [ [ 1096, 1130 ] ], "normalized": [] }, { "id": "1228", "type": "other_name", "text": [ "growth-factor dependent" ], "offsets": [ [ 1141, 1164 ] ], "normalized": [] }, { "id": "1229", "type": "other_name", "text": [ "proliferation" ], "offsets": [ [ 1174, 1187 ] ], "normalized": [] }, { "id": "1230", "type": "other_name", "text": [ "differentiation" ], "offsets": [ [ 1192, 1207 ] ], "normalized": [] }, { "id": "1231", "type": "other_name", "text": [ "granulocytic differentiation" ], "offsets": [ [ 1234, 1262 ] ], "normalized": [] }, { "id": "1232", "type": "other_name", "text": [ "differentiation" ], "offsets": [ [ 1247, 1262 ] ], "normalized": [] }, { "id": "1233", "type": "protein_molecule", "text": [ "granulocyte colony-stimulating factor" ], "offsets": [ [ 1274, 1311 ] ], "normalized": [] }, { "id": "1234", "type": "cell_type", "text": [ "granulocyte" ], "offsets": [ [ 1274, 1285 ] ], "normalized": [] }, { "id": "1235", "type": "other_name", "text": [ "apoptotic cell death" ], "offsets": [ [ 1323, 1343 ] ], "normalized": [] }, { "id": "1236", "type": "protein_molecule", "text": [ "DR-nm23" ], "offsets": [ [ 1390, 1397 ] ], "normalized": [] }, { "id": "1237", "type": "other_name", "text": [ "normal hematopoiesis" ], "offsets": [ [ 1401, 1421 ] ], "normalized": [] }, { "id": "1238", "type": "other_name", "text": [ "overexpression" ], "offsets": [ [ 1457, 1471 ] ], "normalized": [] }, { "id": "1239", "type": "other_name", "text": [ "differentiation arrest" ], "offsets": [ [ 1487, 1509 ] ], "normalized": [] }, { "id": "1240", "type": "other_name", "text": [ "differentiation" ], "offsets": [ [ 1487, 1502 ] ], "normalized": [] }, { "id": "1241", "type": "other_name", "text": [ "blastic transformation" ], "offsets": [ [ 1524, 1546 ] ], "normalized": [] }, { "id": "1242", "type": "other_name", "text": [ "chronic myelogenous leukemia" ], "offsets": [ [ 1550, 1578 ] ], "normalized": [] } ]

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[ { "id": "1244", "type": "title", "text": [ "An interferon-gamma activation sequence mediates the transcriptional regulation of the IgG Fc receptor type IC gene by interferon-gamma." ], "offsets": [ [ 0, 136 ] ] }, { "id": "1245", "type": "abstract", "text": [ "Expression of the IgG Fc receptor type I (Fc gamma RI) on myeloid cells is dramatically increased by treatment with interferon-gamma (IFN-gamma). We observed that Fc gamma RI transcript levels in monoblast-like U937 cells were elevated within 3 hr and peaked 12 hr after exposure to IFN-gamma. Treatment of U937 with IFN-gamma for 9 hr in the presence of cycloheximide led to super-induction of Fc gamma RI expression. Nuclear run-on analysis revealed that the rate of Fc gamma RI transcription was increased by IFN-gamma. Genomic sequence upstream of the Fc gamma RIC gene was cloned and subjected to primer extension analysis, which demonstrated a single transcription initiation site without a TATA box. Transient transfections of CAT reporter gene constructs containing various Fc gamma RIC promoter sequences into U937 cells revealed that a 20-bp region surrounding the transcription start site (-7 to +13) was capable of mediating transcription initiation and that an IFN-gamma responsive element (GIRE) was present within 74 bp upstream of the transcription initiation site. A 17-bp sequence between positions -51 and -35 conferred IFN-gamma responsiveness on a heterologous promoter. Double-stranded GIRE sequence, but not a scrambled sequence, was specifically bound by nuclear proteins from IFN-gamma treated U937 cells. Gel shift experiments further showed that the STAT1 alpha protein bound to the Fc gamma RIC GIRE in response to IFN-gamma treatment of U937 cells. The Fc gamma RIC GIRE is homologous to the IFN-gamma activation sequence (GAS) of the guanylate binding protein and to X box elements of class II MHC genes. Our results demonstrate that transcriptional regulation of the Fc gamma RIC gene by IFN-gamma involves the binding of STAT1 alpha to a 17-bp GAS homology in the proximal promoter." ], "offsets": [ [ 137, 1951 ] ] } ]

[ { "id": "1246", "type": "DNA_domain_or_region", "text": [ "interferon-gamma activation sequence" ], "offsets": [ [ 3, 39 ] ], "normalized": [] }, { "id": "1247", "type": "other_name", "text": [ "transcriptional regulation" ], "offsets": [ [ 53, 79 ] ], "normalized": [] }, { "id": "1248", "type": "DNA_domain_or_region", "text": [ "IgG Fc receptor type IC gene" ], "offsets": [ [ 87, 115 ] ], "normalized": [] }, { "id": "1249", "type": "protein_family_or_group", "text": [ "IgG Fc receptor" ], "offsets": [ [ 87, 102 ] ], "normalized": [] }, { "id": "1250", "type": "protein_molecule", "text": [ "interferon-gamma" ], "offsets": [ [ 3, 19 ] ], "normalized": [] }, { "id": "1251", "type": "protein_molecule", "text": [ "IgG Fc receptor type I" ], "offsets": [ [ 155, 177 ] ], "normalized": [] }, { "id": "1252", "type": "protein_family_or_group", "text": [ "IgG Fc receptor" ], "offsets": [ [ 155, 170 ] ], "normalized": [] }, { "id": "1253", "type": "protein_molecule", "text": [ "Fc gamma RI" ], "offsets": [ [ 179, 190 ] ], "normalized": [] }, { "id": "1254", "type": "cell_type", "text": [ "myeloid cells" ], "offsets": [ [ 195, 208 ] ], "normalized": [] }, { "id": "1255", "type": "protein_molecule", "text": [ "interferon-gamma" ], "offsets": [ [ 253, 269 ] ], "normalized": [] }, { "id": "1256", "type": "protein_molecule", "text": [ "IFN-gamma" ], "offsets": [ [ 271, 280 ] ], "normalized": [] }, { "id": "1257", "type": "other_name", "text": [ "Fc gamma RI transcript levels" ], "offsets": [ [ 300, 329 ] ], "normalized": [] }, { "id": "1258", "type": "protein_molecule", "text": [ "Fc gamma RI" ], "offsets": [ [ 300, 311 ] ], "normalized": [] }, { "id": "1259", "type": "cell_line", "text": [ "monoblast-like U937 cells" ], "offsets": [ [ 333, 358 ] ], "normalized": [] }, { "id": "1260", "type": "protein_molecule", "text": [ "IFN-gamma" ], "offsets": [ [ 420, 429 ] ], "normalized": [] }, { "id": "1261", "type": "cell_line", "text": [ "U937" ], "offsets": [ [ 444, 448 ] ], "normalized": [] }, { "id": "1262", "type": "protein_molecule", "text": [ "IFN-gamma" ], "offsets": [ [ 454, 463 ] ], "normalized": [] }, { "id": "1263", "type": "protein_molecule", "text": [ "Fc gamma RI" ], "offsets": [ [ 532, 543 ] ], "normalized": [] }, { "id": "1264", "type": "protein_molecule", "text": [ "Fc gamma RI" ], "offsets": [ [ 606, 617 ] ], "normalized": [] }, { "id": "1265", "type": "protein_molecule", "text": [ "IFN-gamma" ], "offsets": [ [ 649, 658 ] ], "normalized": [] }, { "id": "1266", "type": "DNA_domain_or_region", "text": [ "Fc gamma RIC gene" ], "offsets": [ [ 693, 710 ] ], "normalized": [] }, { "id": "1267", "type": "other_name", "text": [ "primer extension analysis" ], "offsets": [ [ 739, 764 ] ], "normalized": [] }, { "id": "1268", "type": "DNA_domain_or_region", "text": [ "transcription initiation site" ], "offsets": [ [ 794, 823 ] ], "normalized": [] }, { "id": "1269", "type": "DNA_domain_or_region", "text": [ "TATA box" ], "offsets": [ [ 834, 842 ] ], "normalized": [] }, { "id": "1270", "type": "DNA_family_or_group", "text": [ "CAT reporter gene constructs" ], "offsets": [ [ 871, 899 ] ], "normalized": [] }, { "id": "1271", "type": "DNA_family_or_group", "text": [ "reporter gene constructs" ], "offsets": [ [ 875, 899 ] ], "normalized": [] }, { "id": "1272", "type": "DNA_domain_or_region", "text": [ "Fc gamma RIC promoter sequences" ], "offsets": [ [ 919, 950 ] ], "normalized": [] }, { "id": "1273", "type": "cell_line", "text": [ "U937 cells" ], "offsets": [ [ 956, 966 ] ], "normalized": [] }, { "id": "1274", "type": "DNA_domain_or_region", "text": [ "20-bp region" ], "offsets": [ [ 983, 995 ] ], "normalized": [] }, { "id": "1275", "type": "DNA_domain_or_region", "text": [ "transcription start site" ], "offsets": [ [ 1012, 1036 ] ], "normalized": [] }, { "id": "1276", "type": "other_name", "text": [ "transcription initiation" ], "offsets": [ [ 1074, 1098 ] ], "normalized": [] }, { "id": "1277", "type": "DNA_domain_or_region", "text": [ "IFN-gamma responsive element" ], "offsets": [ [ 1111, 1139 ] ], "normalized": [] }, { "id": "1278", "type": "DNA_domain_or_region", "text": [ "GIRE" ], "offsets": [ [ 1141, 1145 ] ], "normalized": [] }, { "id": "1279", "type": "DNA_domain_or_region", "text": [ "74 bp upstream" ], "offsets": [ [ 1166, 1180 ] ], "normalized": [] }, { "id": "1280", "type": "DNA_domain_or_region", "text": [ "transcription initiation site" ], "offsets": [ [ 1188, 1217 ] ], "normalized": [] }, { "id": "1281", "type": "other_name", "text": [ "transcription initiation" ], "offsets": [ [ 1188, 1212 ] ], "normalized": [] }, { "id": "1282", "type": "DNA_domain_or_region", "text": [ "17-bp sequence" ], "offsets": [ [ 1221, 1235 ] ], "normalized": [] }, { "id": "1283", "type": "other_name", "text": [ "IFN-gamma responsiveness" ], "offsets": [ [ 1276, 1300 ] ], "normalized": [] }, { "id": "1284", "type": "protein_molecule", "text": [ "IFN-gamma" ], "offsets": [ [ 1276, 1285 ] ], "normalized": [] }, { "id": "1285", "type": "DNA_domain_or_region", "text": [ "heterologous promoter" ], "offsets": [ [ 1306, 1327 ] ], "normalized": [] }, { "id": "1286", "type": "DNA_domain_or_region", "text": [ "Double-stranded GIRE sequence" ], "offsets": [ [ 1329, 1358 ] ], "normalized": [] }, { "id": "1287", "type": "DNA_family_or_group", "text": [ "scrambled sequence" ], "offsets": [ [ 1370, 1388 ] ], "normalized": [] }, { "id": "1288", "type": "protein_family_or_group", "text": [ "nuclear proteins" ], "offsets": [ [ 1416, 1432 ] ], "normalized": [] }, { "id": "1289", "type": "cell_line", "text": [ "IFN-gamma treated U937 cells" ], "offsets": [ [ 1438, 1466 ] ], "normalized": [] }, { "id": "1290", "type": "protein_molecule", "text": [ "IFN-gamma" ], "offsets": [ [ 1438, 1447 ] ], "normalized": [] }, { "id": "1291", "type": "cell_line", "text": [ "U937 cells" ], "offsets": [ [ 1456, 1466 ] ], "normalized": [] }, { "id": "1292", "type": "protein_molecule", "text": [ "STAT1 alpha protein" ], "offsets": [ [ 1514, 1533 ] ], "normalized": [] }, { "id": "1293", "type": "DNA_domain_or_region", "text": [ "Fc gamma RIC GIRE" ], "offsets": [ [ 1547, 1564 ] ], "normalized": [] }, { "id": "1294", "type": "other_name", "text": [ "IFN-gamma treatment" ], "offsets": [ [ 1580, 1599 ] ], "normalized": [] }, { "id": "1295", "type": "protein_molecule", "text": [ "IFN-gamma" ], "offsets": [ [ 1580, 1589 ] ], "normalized": [] }, { "id": "1296", "type": "cell_line", "text": [ "U937 cells" ], "offsets": [ [ 1603, 1613 ] ], "normalized": [] }, { "id": "1297", "type": "DNA_domain_or_region", "text": [ "Fc gamma RIC GIRE" ], "offsets": [ [ 1619, 1636 ] ], "normalized": [] }, { "id": "1298", "type": "DNA_domain_or_region", "text": [ "IFN-gamma activation sequence" ], "offsets": [ [ 1658, 1687 ] ], "normalized": [] }, { "id": "1299", "type": "protein_molecule", "text": [ "IFN-gamma" ], "offsets": [ [ 1658, 1667 ] ], "normalized": [] }, { "id": "1300", "type": "DNA_domain_or_region", "text": [ "GAS" ], "offsets": [ [ 1689, 1692 ] ], "normalized": [] }, { "id": "1301", "type": "protein_molecule", "text": [ "guanylate binding protein" ], "offsets": [ [ 1701, 1726 ] ], "normalized": [] }, { "id": "1302", "type": "DNA_family_or_group", "text": [ "X box elements" ], "offsets": [ [ 1734, 1748 ] ], "normalized": [] }, { "id": "1303", "type": "DNA_family_or_group", "text": [ "class II MHC genes" ], "offsets": [ [ 1752, 1770 ] ], "normalized": [] }, { "id": "1304", "type": "other_name", "text": [ "transcriptional regulation" ], "offsets": [ [ 1801, 1827 ] ], "normalized": [] }, { "id": "1305", "type": "DNA_domain_or_region", "text": [ "Fc gamma RIC gene" ], "offsets": [ [ 1835, 1852 ] ], "normalized": [] }, { "id": "1306", "type": "protein_molecule", "text": [ "IFN-gamma" ], "offsets": [ [ 1856, 1865 ] ], "normalized": [] }, { "id": "1307", "type": "protein_molecule", "text": [ "STAT1 alpha" ], "offsets": [ [ 1890, 1901 ] ], "normalized": [] }, { "id": "1308", "type": "DNA_domain_or_region", "text": [ "17-bp GAS homology" ], "offsets": [ [ 1907, 1925 ] ], "normalized": [] }, { "id": "1309", "type": "DNA_domain_or_region", "text": [ "proximal promoter" ], "offsets": [ [ 1933, 1950 ] ], "normalized": [] } ]

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[ { "id": "1311", "type": "title", "text": [ "Constitutively activated Jak-STAT pathway in T cells transformed with HTLV-I." ], "offsets": [ [ 0, 77 ] ] }, { "id": "1312", "type": "abstract", "text": [ "Human T cell lymphotropic virus I (HTLV-I) is the etiological agent for adult T cell leukemia and tropical spastic paraparesis (also termed HTLV-I-associated myelopathy). HTLV-I-infected peripheral blood T cells exhibit an initial phase of interleukin-2 (IL-2)-dependent growth; over time, by an unknown mechanism, the cells become IL-2-independent. Whereas the Jak kinases Jak1 and Jak3 and the signal transducer and activator of transcription proteins Stat3 and Stat5 are activated in normal T cells in response to IL-2, this signaling pathway was constitutively activated in HTLV-I-transformed cells. In HTLV-I-infected cord blood lymphocytes, the transition from IL-2-dependent to IL-2-independent growth correlated with the acquisition of a constitutively activated Jak-STAT pathway, which suggests that this pathway participates in HTLV-I-mediated T cell transformation." ], "offsets": [ [ 78, 954 ] ] } ]

[ { "id": "1313", "type": "other_name", "text": [ "Jak-STAT pathway" ], "offsets": [ [ 25, 41 ] ], "normalized": [] }, { "id": "1314", "type": "protein_family_or_group", "text": [ "Jak" ], "offsets": [ [ 25, 28 ] ], "normalized": [] }, { "id": "1315", "type": "protein_family_or_group", "text": [ "-STAT" ], "offsets": [ [ 28, 33 ] ], "normalized": [] }, { "id": "1316", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 45, 52 ] ], "normalized": [] }, { "id": "1317", "type": "virus", "text": [ "HTLV-I" ], "offsets": [ [ 70, 76 ] ], "normalized": [] }, { "id": "1318", "type": "virus", "text": [ "Human T cell lymphotropic virus I" ], "offsets": [ [ 78, 111 ] ], "normalized": [] }, { "id": "1319", "type": "virus", "text": [ "HTLV-I" ], "offsets": [ [ 113, 119 ] ], "normalized": [] }, { "id": "1320", "type": "other_name", "text": [ "etiological agent" ], "offsets": [ [ 128, 145 ] ], "normalized": [] }, { "id": "1321", "type": "other_name", "text": [ "adult T cell leukemia" ], "offsets": [ [ 150, 171 ] ], "normalized": [] }, { "id": "1322", "type": "other_name", "text": [ "tropical spastic paraparesis" ], "offsets": [ [ 176, 204 ] ], "normalized": [] }, { "id": "1323", "type": "other_name", "text": [ "HTLV-I-associated myelopathy" ], "offsets": [ [ 218, 246 ] ], "normalized": [] }, { "id": "1324", "type": "virus", "text": [ "HTLV-I" ], "offsets": [ [ 218, 224 ] ], "normalized": [] }, { "id": "1325", "type": "cell_type", "text": [ "HTLV-I-infected peripheral blood T cells" ], "offsets": [ [ 249, 289 ] ], "normalized": [] }, { "id": "1326", "type": "virus", "text": [ "HTLV-I" ], "offsets": [ [ 249, 255 ] ], "normalized": [] }, { "id": "1327", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 282, 289 ] ], "normalized": [] }, { "id": "1328", "type": "other_name", "text": [ "interleukin-2 (IL-2)-dependent growth" ], "offsets": [ [ 318, 355 ] ], "normalized": [] }, { "id": "1329", "type": "protein_molecule", "text": [ "interleukin-2" ], "offsets": [ [ 318, 331 ] ], "normalized": [] }, { "id": "1330", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 333, 337 ] ], "normalized": [] }, { "id": "1331", "type": "other_name", "text": [ "IL-2-independent" ], "offsets": [ [ 410, 426 ] ], "normalized": [] }, { "id": "1332", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 410, 414 ] ], "normalized": [] }, { "id": "1333", "type": "protein_family_or_group", "text": [ "Jak kinases" ], "offsets": [ [ 440, 451 ] ], "normalized": [] }, { "id": "1334", "type": "protein_molecule", "text": [ "Jak1" ], "offsets": [ [ 452, 456 ] ], "normalized": [] }, { "id": "1335", "type": "protein_molecule", "text": [ "Jak3" ], "offsets": [ [ 461, 465 ] ], "normalized": [] }, { "id": "1336", "type": "protein_family_or_group", "text": [ "transcription proteins" ], "offsets": [ [ 509, 531 ] ], "normalized": [] }, { "id": "1337", "type": "protein_molecule", "text": [ "Stat3" ], "offsets": [ [ 532, 537 ] ], "normalized": [] }, { "id": "1338", "type": "protein_molecule", "text": [ "Stat5" ], "offsets": [ [ 542, 547 ] ], "normalized": [] }, { "id": "1339", "type": "cell_type", "text": [ "normal T cells" ], "offsets": [ [ 565, 579 ] ], "normalized": [] }, { "id": "1340", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 572, 579 ] ], "normalized": [] }, { "id": "1341", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 595, 599 ] ], "normalized": [] }, { "id": "1342", "type": "cell_line", "text": [ "HTLV-I-transformed cells" ], "offsets": [ [ 656, 680 ] ], "normalized": [] }, { "id": "1343", "type": "virus", "text": [ "HTLV-I" ], "offsets": [ [ 656, 662 ] ], "normalized": [] }, { "id": "1344", "type": "cell_line", "text": [ "HTLV-I-infected cord blood lymphocytes" ], "offsets": [ [ 685, 723 ] ], "normalized": [] }, { "id": "1345", "type": "virus", "text": [ "HTLV-I" ], "offsets": [ [ 685, 691 ] ], "normalized": [] }, { "id": "1346", "type": "other_name", "text": [ "IL-2-dependent" ], "offsets": [ [ 745, 759 ] ], "normalized": [] }, { "id": "1347", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 745, 749 ] ], "normalized": [] }, { "id": "1348", "type": "other_name", "text": [ "IL-2-independent growth" ], "offsets": [ [ 763, 786 ] ], "normalized": [] }, { "id": "1349", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 763, 767 ] ], "normalized": [] }, { "id": "1350", "type": "other_name", "text": [ "Jak-STAT pathway" ], "offsets": [ [ 849, 865 ] ], "normalized": [] }, { "id": "1351", "type": "protein_family_or_group", "text": [ "Jak" ], "offsets": [ [ 849, 852 ] ], "normalized": [] }, { "id": "1352", "type": "protein_family_or_group", "text": [ "-STAT" ], "offsets": [ [ 852, 857 ] ], "normalized": [] }, { "id": "1353", "type": "other_name", "text": [ "HTLV-I-mediated T cell transformation" ], "offsets": [ [ 916, 953 ] ], "normalized": [] }, { "id": "1354", "type": "virus", "text": [ "HTLV-I" ], "offsets": [ [ 916, 922 ] ], "normalized": [] } ]

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[ { "id": "1356", "type": "title", "text": [ "Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines." ], "offsets": [ [ 0, 172 ] ] }, { "id": "1357", "type": "abstract", "text": [ "To test the hypothesis that nitric oxide (NO) limits endothelial activation, we treated cytokine-stimulated human saphenous vein endothelial cells with several NO donors and assessed their effects on the inducible expression of vascular cell adhesion molecule-1 (VCAM-1). In a concentration-dependent manner, NO inhibited interleukin (IL)-1 alpha-stimulated VCAM-1 expression by 35-55% as determined by cell surface enzyme immunoassays and flow cytometry. This inhibition was paralleled by reduced monocyte adhesion to endothelial monolayers in nonstatic assays, was unaffected by cGMP analogues, and was quantitatively similar after stimulation by either IL-1 alpha, IL-1 beta, IL-4, tumor necrosis factor (TNF alpha), or bacterial lipopolysaccharide. NO also decreased the endothelial expression of other leukocyte adhesion molecules (E-selectin and to a lesser extent, intercellular adhesion molecule-1) and secretable cytokines (IL-6 and IL-8). Inhibition of endogenous NO production by L-N-monomethyl-arginine also induced the expression of VCAM-1, but did not augment cytokine-induced VCAM-1 expression. Nuclear run-on assays, transfection studies using various VCAM-1 promoter reporter gene constructs, and electrophoretic mobility shift assays indicated that NO represses VCAM-1 gene transcription, in part, by inhibiting NF-kappa B. We propose that NO's ability to limit endothelial activation and inhibit monocyte adhesion may contribute to some of its antiatherogenic and antiinflammatory properties within the vessel wall." ], "offsets": [ [ 173, 1707 ] ] } ]

[ { "id": "1358", "type": "inorganic", "text": [ "Nitric oxide" ], "offsets": [ [ 0, 12 ] ], "normalized": [] }, { "id": "1359", "type": "other_name", "text": [ "cytokine-induced endothelial activation" ], "offsets": [ [ 23, 62 ] ], "normalized": [] }, { "id": "1360", "type": "protein_family_or_group", "text": [ "cytokine" ], "offsets": [ [ 23, 31 ] ], "normalized": [] }, { "id": "1361", "type": "inorganic", "text": [ "Nitric oxide" ], "offsets": [ [ 64, 76 ] ], "normalized": [] }, { "id": "1362", "type": "other_name", "text": [ "endothelial expression" ], "offsets": [ [ 97, 119 ] ], "normalized": [] }, { "id": "1363", "type": "protein_family_or_group", "text": [ "adhesion molecules" ], "offsets": [ [ 123, 141 ] ], "normalized": [] }, { "id": "1364", "type": "protein_family_or_group", "text": [ "proinflammatory cytokines" ], "offsets": [ [ 146, 171 ] ], "normalized": [] }, { "id": "1365", "type": "inorganic", "text": [ "nitric oxide" ], "offsets": [ [ 201, 213 ] ], "normalized": [] }, { "id": "1366", "type": "inorganic", "text": [ "NO" ], "offsets": [ [ 215, 217 ] ], "normalized": [] }, { "id": "1367", "type": "other_name", "text": [ "endothelial activation" ], "offsets": [ [ 226, 248 ] ], "normalized": [] }, { "id": "1368", "type": "cell_line", "text": [ "cytokine-stimulated human saphenous vein endothelial cells" ], "offsets": [ [ 261, 319 ] ], "normalized": [] }, { "id": "1369", "type": "inorganic", "text": [ "NO donors" ], "offsets": [ [ 333, 342 ] ], "normalized": [] }, { "id": "1370", "type": "inorganic", "text": [ "NO" ], "offsets": [ [ 333, 335 ] ], "normalized": [] }, { "id": "1371", "type": "protein_molecule", "text": [ "vascular cell adhesion molecule-1" ], "offsets": [ [ 401, 434 ] ], "normalized": [] }, { "id": "1372", "type": "protein_molecule", "text": [ "VCAM-1" ], "offsets": [ [ 436, 442 ] ], "normalized": [] }, { "id": "1373", "type": "other_name", "text": [ "concentration-dependent manner" ], "offsets": [ [ 450, 480 ] ], "normalized": [] }, { "id": "1374", "type": "inorganic", "text": [ "NO" ], "offsets": [ [ 482, 484 ] ], "normalized": [] }, { "id": "1375", "type": "other_name", "text": [ "interleukin (IL)-1 alpha-stimulated VCAM-1 expression" ], "offsets": [ [ 495, 548 ] ], "normalized": [] }, { "id": "1376", "type": "protein_molecule", "text": [ "interleukin (IL)-1" ], "offsets": [ [ 495, 513 ] ], "normalized": [] }, { "id": "1377", "type": "protein_molecule", "text": [ "VCAM-1" ], "offsets": [ [ 531, 537 ] ], "normalized": [] }, { "id": "1378", "type": "other_name", "text": [ "cell surface enzyme immunoassays" ], "offsets": [ [ 576, 608 ] ], "normalized": [] }, { "id": "1379", "type": "other_name", "text": [ "flow cytometry" ], "offsets": [ [ 613, 627 ] ], "normalized": [] }, { "id": "1380", "type": "other_name", "text": [ "monocyte adhesion" ], "offsets": [ [ 671, 688 ] ], "normalized": [] }, { "id": "1381", "type": "other_name", "text": [ "endothelial monolayers" ], "offsets": [ [ 692, 714 ] ], "normalized": [] }, { "id": "1382", "type": "other_name", "text": [ "nonstatic assays" ], "offsets": [ [ 718, 734 ] ], "normalized": [] }, { "id": "1383", "type": "other_organic_compound", "text": [ "cGMP analogues" ], "offsets": [ [ 754, 768 ] ], "normalized": [] }, { "id": "1384", "type": "protein_family_or_group", "text": [ "IL-1 alpha" ], "offsets": [ [ 829, 839 ] ], "normalized": [] }, { "id": "1385", "type": "protein_molecule", "text": [ "IL-1 beta" ], "offsets": [ [ 841, 850 ] ], "normalized": [] }, { "id": "1386", "type": "protein_molecule", "text": [ "IL-4" ], "offsets": [ [ 852, 856 ] ], "normalized": [] }, { "id": "1387", "type": "protein_family_or_group", "text": [ "tumor necrosis factor" ], "offsets": [ [ 858, 879 ] ], "normalized": [] }, { "id": "1388", "type": "protein_molecule", "text": [ "TNF alpha" ], "offsets": [ [ 881, 890 ] ], "normalized": [] }, { "id": "1389", "type": "lipid", "text": [ "bacterial lipopolysaccharide" ], "offsets": [ [ 896, 924 ] ], "normalized": [] }, { "id": "1390", "type": "inorganic", "text": [ "NO" ], "offsets": [ [ 926, 928 ] ], "normalized": [] }, { "id": "1391", "type": "other_name", "text": [ "endothelial expression" ], "offsets": [ [ 948, 970 ] ], "normalized": [] }, { "id": "1392", "type": "protein_family_or_group", "text": [ "leukocyte adhesion molecules" ], "offsets": [ [ 980, 1008 ] ], "normalized": [] }, { "id": "1393", "type": "protein_family_or_group", "text": [ "adhesion molecules" ], "offsets": [ [ 990, 1008 ] ], "normalized": [] }, { "id": "1394", "type": "protein_molecule", "text": [ "E-selectin" ], "offsets": [ [ 1010, 1020 ] ], "normalized": [] }, { "id": "1395", "type": "protein_molecule", "text": [ "intercellular adhesion molecule-1" ], "offsets": [ [ 1045, 1078 ] ], "normalized": [] }, { "id": "1396", "type": "protein_family_or_group", "text": [ "cytokines" ], "offsets": [ [ 1095, 1104 ] ], "normalized": [] }, { "id": "1397", "type": "protein_molecule", "text": [ "IL-6" ], "offsets": [ [ 1106, 1110 ] ], "normalized": [] }, { "id": "1398", "type": "protein_molecule", "text": [ "IL-8" ], "offsets": [ [ 1115, 1119 ] ], "normalized": [] }, { "id": "1399", "type": "inorganic", "text": [ "NO" ], "offsets": [ [ 1147, 1149 ] ], "normalized": [] }, { "id": "1400", "type": "amino_acid_monomer", "text": [ "L-N-monomethyl-arginine" ], "offsets": [ [ 1164, 1187 ] ], "normalized": [] }, { "id": "1401", "type": "protein_molecule", "text": [ "VCAM-1" ], "offsets": [ [ 1219, 1225 ] ], "normalized": [] }, { "id": "1402", "type": "other_name", "text": [ "cytokine-induced VCAM-1 expression" ], "offsets": [ [ 1247, 1281 ] ], "normalized": [] }, { "id": "1403", "type": "protein_molecule", "text": [ "VCAM-1" ], "offsets": [ [ 1264, 1270 ] ], "normalized": [] }, { "id": "1404", "type": "other_name", "text": [ "Nuclear run-on assays" ], "offsets": [ [ 1283, 1304 ] ], "normalized": [] }, { "id": "1405", "type": "other_name", "text": [ "transfection studies" ], "offsets": [ [ 1306, 1326 ] ], "normalized": [] }, { "id": "1406", "type": "DNA_domain_or_region", "text": [ "VCAM-1 promoter reporter gene constructs" ], "offsets": [ [ 1341, 1381 ] ], "normalized": [] }, { "id": "1407", "type": "protein_molecule", "text": [ "VCAM-1" ], "offsets": [ [ 1341, 1347 ] ], "normalized": [] }, { "id": "1408", "type": "DNA_family_or_group", "text": [ "reporter gene constructs" ], "offsets": [ [ 1357, 1381 ] ], "normalized": [] }, { "id": "1409", "type": "other_name", "text": [ "electrophoretic mobility shift assays" ], "offsets": [ [ 1387, 1424 ] ], "normalized": [] }, { "id": "1410", "type": "inorganic", "text": [ "NO" ], "offsets": [ [ 1440, 1442 ] ], "normalized": [] }, { "id": "1411", "type": "other_name", "text": [ "VCAM-1 gene transcription" ], "offsets": [ [ 1453, 1478 ] ], "normalized": [] }, { "id": "1412", "type": "protein_molecule", "text": [ "VCAM-1" ], "offsets": [ [ 1453, 1459 ] ], "normalized": [] }, { "id": "1413", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 1503, 1513 ] ], "normalized": [] }, { "id": "1414", "type": "inorganic", "text": [ "NO" ], "offsets": [ [ 1531, 1533 ] ], "normalized": [] }, { "id": "1415", "type": "other_name", "text": [ "endothelial activation" ], "offsets": [ [ 1553, 1575 ] ], "normalized": [] }, { "id": "1416", "type": "other_name", "text": [ "monocyte adhesion" ], "offsets": [ [ 1588, 1605 ] ], "normalized": [] }, { "id": "1417", "type": "(AND other_name other_name)", "text": [ "antiatherogenic and antiinflammatory properties" ], "offsets": [ [ 1636, 1683 ] ], "normalized": [] }, { "id": "1418", "type": "", "text": [ "antiatherogenic" ], "offsets": [ [ 1636, 1651 ] ], "normalized": [] }, { "id": "1419", "type": "", "text": [ "antiinflammatory" ], "offsets": [ [ 1656, 1672 ] ], "normalized": [] }, { "id": "1420", "type": "", "text": [ "properties" ], "offsets": [ [ 1673, 1683 ] ], "normalized": [] }, { "id": "1421", "type": "tissue", "text": [ "vessel wall" ], "offsets": [ [ 1695, 1706 ] ], "normalized": [] } ]

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[ { "id": "1423", "type": "title", "text": [ "MIP1 alpha nuclear protein (MNP), a novel transcription factor expressed in hematopoietic cells that is crucial for transcription of the human MIP-1 alpha gene." ], "offsets": [ [ 0, 160 ] ] }, { "id": "1424", "type": "abstract", "text": [ "Murine macrophage inflammatory protein 1 alpha (MIP-1 alpha) and its human equivalent (GOS19, LD78, or AT464) are members of the -C-C family of low-molecular-weight chemokines. Secreted from activated T cells and macrophages, bone marrow-derived MIP-1 alpha/GOS19 inhibits primitive hematopoietic stem cells and appears to be involved in the homeostatic control of stem cell proliferation. It also induces chemotaxis and inflammatory responses in mature cell types. Therefore, it is important to understand the mechanisms which control the expression of MIP-1 alpha/GOS19. Previous work has shown that in Jurkat T cells, a set of widely expressed transcription factors (the ICK-1 family) affect the GOS19 promoter. One member, ICK-1A, behaves as a strong negative regulator. In this communication, we provide evidence that the pathway of induction in the macrophage cell line U937 is different from that in Jurkat cells. Furthermore, we show that the ICK-1 binding site does not confer negative regulation in U937 cells. We provide evidence for an additional binding site, the MIP-1 alpha nuclear protein (MNP) site, which overlaps the ICK-1 site. Interaction of nuclear extracts from various cell lines and tissue with the MNP site leads to the formation of fast-migrating protein-DNA complexes with similar but distinct electrophoretic mobilities. A mutation of the MNP site which does not abrogate ICK-1 binding inactivates the GOS19.1 promoter in U937 cells and reduces its activity by fourfold in Jurkat cells. We propose that the MNP protein(s) binding at the MNP site constitutes a novel transcription factor(s) expressed in hematopoietic cells." ], "offsets": [ [ 161, 1813 ] ] } ]

[ { "id": "1425", "type": "protein_molecule", "text": [ "MIP1 alpha nuclear protein" ], "offsets": [ [ 0, 26 ] ], "normalized": [] }, { "id": "1426", "type": "protein_molecule", "text": [ "MNP" ], "offsets": [ [ 28, 31 ] ], "normalized": [] }, { "id": "1427", "type": "protein_family_or_group", "text": [ "transcription factor" ], "offsets": [ [ 42, 62 ] ], "normalized": [] }, { "id": "1428", "type": "other_name", "text": [ "transcription" ], "offsets": [ [ 42, 55 ] ], "normalized": [] }, { "id": "1429", "type": "DNA_domain_or_region", "text": [ "human MIP-1 alpha gene" ], "offsets": [ [ 137, 159 ] ], "normalized": [] }, { "id": "1430", "type": "protein_molecule", "text": [ "Murine macrophage inflammatory protein 1 alpha" ], "offsets": [ [ 161, 207 ] ], "normalized": [] }, { "id": "1431", "type": "protein_molecule", "text": [ "MIP-1 alpha" ], "offsets": [ [ 209, 220 ] ], "normalized": [] }, { "id": "1432", "type": "protein_family_or_group", "text": [ "human equivalent" ], "offsets": [ [ 230, 246 ] ], "normalized": [] }, { "id": "1433", "type": "protein_molecule", "text": [ "GOS19" ], "offsets": [ [ 248, 253 ] ], "normalized": [] }, { "id": "1434", "type": "protein_molecule", "text": [ "LD78" ], "offsets": [ [ 255, 259 ] ], "normalized": [] }, { "id": "1435", "type": "protein_molecule", "text": [ "AT464" ], "offsets": [ [ 264, 269 ] ], "normalized": [] }, { "id": "1436", "type": "protein_family_or_group", "text": [ "-C-C family" ], "offsets": [ [ 290, 301 ] ], "normalized": [] }, { "id": "1437", "type": "protein_domain_or_region", "text": [ "low-molecular-weight chemokines" ], "offsets": [ [ 305, 336 ] ], "normalized": [] }, { "id": "1438", "type": "cell_type", "text": [ "activated T cells" ], "offsets": [ [ 352, 369 ] ], "normalized": [] }, { "id": "1439", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 362, 369 ] ], "normalized": [] }, { "id": "1440", "type": "cell_type", "text": [ "macrophages" ], "offsets": [ [ 374, 385 ] ], "normalized": [] }, { "id": "1441", "type": "protein_molecule", "text": [ "marrow-derived MIP-1 alpha/GOS19" ], "offsets": [ [ 392, 424 ] ], "normalized": [] }, { "id": "1442", "type": "protein_molecule", "text": [ "MIP-1 alpha" ], "offsets": [ [ 407, 418 ] ], "normalized": [] }, { "id": "1443", "type": "protein_molecule", "text": [ "/GOS19" ], "offsets": [ [ 418, 424 ] ], "normalized": [] }, { "id": "1444", "type": "cell_type", "text": [ "primitive hematopoietic stem cells" ], "offsets": [ [ 434, 468 ] ], "normalized": [] }, { "id": "1445", "type": "other_name", "text": [ "stem cell proliferation" ], "offsets": [ [ 526, 549 ] ], "normalized": [] }, { "id": "1446", "type": "cell_type", "text": [ "stem cell" ], "offsets": [ [ 458, 467 ] ], "normalized": [] }, { "id": "1447", "type": "other_name", "text": [ "proliferation" ], "offsets": [ [ 536, 549 ] ], "normalized": [] }, { "id": "1448", "type": "other_name", "text": [ "chemotaxis" ], "offsets": [ [ 567, 577 ] ], "normalized": [] }, { "id": "1449", "type": "other_name", "text": [ "inflammatory responses" ], "offsets": [ [ 582, 604 ] ], "normalized": [] }, { "id": "1450", "type": "cell_type", "text": [ "mature cell types" ], "offsets": [ [ 608, 625 ] ], "normalized": [] }, { "id": "1451", "type": "protein_molecule", "text": [ "MIP-1 alpha" ], "offsets": [ [ 715, 726 ] ], "normalized": [] }, { "id": "1452", "type": "protein_molecule", "text": [ "/GOS19" ], "offsets": [ [ 726, 732 ] ], "normalized": [] }, { "id": "1453", "type": "cell_line", "text": [ "Jurkat T cells" ], "offsets": [ [ 766, 780 ] ], "normalized": [] }, { "id": "1454", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 773, 780 ] ], "normalized": [] }, { "id": "1455", "type": "protein_family_or_group", "text": [ "transcription factors" ], "offsets": [ [ 808, 829 ] ], "normalized": [] }, { "id": "1456", "type": "protein_domain_or_region", "text": [ "ICK-1 family" ], "offsets": [ [ 835, 847 ] ], "normalized": [] }, { "id": "1457", "type": "DNA_domain_or_region", "text": [ "GOS19 promoter" ], "offsets": [ [ 860, 874 ] ], "normalized": [] }, { "id": "1458", "type": "protein_molecule", "text": [ "GOS19" ], "offsets": [ [ 860, 865 ] ], "normalized": [] }, { "id": "1459", "type": "protein_molecule", "text": [ "ICK-1A" ], "offsets": [ [ 888, 894 ] ], "normalized": [] }, { "id": "1460", "type": "protein_family_or_group", "text": [ "strong negative regulator" ], "offsets": [ [ 909, 934 ] ], "normalized": [] }, { "id": "1461", "type": "cell_line", "text": [ "macrophage cell line" ], "offsets": [ [ 1016, 1036 ] ], "normalized": [] }, { "id": "1462", "type": "cell_line", "text": [ "U937" ], "offsets": [ [ 1037, 1041 ] ], "normalized": [] }, { "id": "1463", "type": "cell_line", "text": [ "Jurkat cells" ], "offsets": [ [ 1068, 1080 ] ], "normalized": [] }, { "id": "1464", "type": "DNA_domain_or_region", "text": [ "ICK-1 binding site" ], "offsets": [ [ 1112, 1130 ] ], "normalized": [] }, { "id": "1465", "type": "other_name", "text": [ "negative regulation" ], "offsets": [ [ 1147, 1166 ] ], "normalized": [] }, { "id": "1466", "type": "cell_line", "text": [ "U937 cells" ], "offsets": [ [ 1170, 1180 ] ], "normalized": [] }, { "id": "1467", "type": "DNA_domain_or_region", "text": [ "binding site" ], "offsets": [ [ 1220, 1232 ] ], "normalized": [] }, { "id": "1468", "type": "DNA_domain_or_region", "text": [ "MIP-1 alpha nuclear protein (MNP) site" ], "offsets": [ [ 1238, 1276 ] ], "normalized": [] }, { "id": "1469", "type": "protein_molecule", "text": [ "MIP-1 alpha" ], "offsets": [ [ 1238, 1249 ] ], "normalized": [] }, { "id": "1470", "type": "DNA_domain_or_region", "text": [ "ICK-1 site" ], "offsets": [ [ 1297, 1307 ] ], "normalized": [] }, { "id": "1471", "type": "cell_component", "text": [ "nuclear extracts" ], "offsets": [ [ 1324, 1340 ] ], "normalized": [] }, { "id": "1472", "type": "cell_line", "text": [ "various cell lines" ], "offsets": [ [ 1346, 1364 ] ], "normalized": [] }, { "id": "1473", "type": "tissue", "text": [ "tissue" ], "offsets": [ [ 1369, 1375 ] ], "normalized": [] }, { "id": "1474", "type": "DNA_domain_or_region", "text": [ "MNP site" ], "offsets": [ [ 1385, 1393 ] ], "normalized": [] }, { "id": "1475", "type": "protein_complex", "text": [ "fast-migrating protein-DNA complexes" ], "offsets": [ [ 1420, 1456 ] ], "normalized": [] }, { "id": "1476", "type": "other_name", "text": [ "electrophoretic mobilities" ], "offsets": [ [ 1483, 1509 ] ], "normalized": [] }, { "id": "1477", "type": "DNA_domain_or_region", "text": [ "MNP site" ], "offsets": [ [ 1529, 1537 ] ], "normalized": [] }, { "id": "1478", "type": "other_name", "text": [ "ICK-1 binding" ], "offsets": [ [ 1562, 1575 ] ], "normalized": [] }, { "id": "1479", "type": "DNA_domain_or_region", "text": [ "GOS19.1 promoter" ], "offsets": [ [ 1592, 1608 ] ], "normalized": [] }, { "id": "1480", "type": "cell_line", "text": [ "U937 cells" ], "offsets": [ [ 1612, 1622 ] ], "normalized": [] }, { "id": "1481", "type": "cell_line", "text": [ "Jurkat cells" ], "offsets": [ [ 1663, 1675 ] ], "normalized": [] }, { "id": "1482", "type": "protein_family_or_group", "text": [ "MNP protein" ], "offsets": [ [ 1697, 1708 ] ], "normalized": [] }, { "id": "1483", "type": "DNA_domain_or_region", "text": [ "MNP site" ], "offsets": [ [ 1727, 1735 ] ], "normalized": [] }, { "id": "1484", "type": "protein_family_or_group", "text": [ "transcription factor" ], "offsets": [ [ 1756, 1776 ] ], "normalized": [] }, { "id": "1485", "type": "cell_type", "text": [ "hematopoietic cells" ], "offsets": [ [ 1793, 1812 ] ], "normalized": [] } ]

[]

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[ { "id": "1487", "type": "title", "text": [ "The effect of Toremifene on the expression of some genes in human mononuclear cells." ], "offsets": [ [ 0, 84 ] ] }, { "id": "1488", "type": "abstract", "text": [ "Toremifene exerts multiple and varied effects on the gene expression of human peripheral mononuclear cells. After short-term, in vitro exposure to therapeutical levels, distinct changes in P-glycoprotein, steroid receptors, p53 and Bcl-2 expression take place. In view of the increasing use of antiestrogens in cancer therapy and prevention, there is obvious merit in long-term in vivo studies to be conducted." ], "offsets": [ [ 85, 495 ] ] } ]

[ { "id": "1489", "type": "other_organic_compound", "text": [ "Toremifene" ], "offsets": [ [ 14, 24 ] ], "normalized": [] }, { "id": "1490", "type": "cell_type", "text": [ "human mononuclear cells" ], "offsets": [ [ 60, 83 ] ], "normalized": [] }, { "id": "1491", "type": "other_organic_compound", "text": [ "Toremifene" ], "offsets": [ [ 85, 95 ] ], "normalized": [] }, { "id": "1492", "type": "other_name", "text": [ "gene expression" ], "offsets": [ [ 138, 153 ] ], "normalized": [] }, { "id": "1493", "type": "cell_type", "text": [ "human peripheral mononuclear cells" ], "offsets": [ [ 157, 191 ] ], "normalized": [] }, { "id": "1494", "type": "other_name", "text": [ "vitro exposure" ], "offsets": [ [ 214, 228 ] ], "normalized": [] }, { "id": "1495", "type": "other_name", "text": [ "therapeutical levels" ], "offsets": [ [ 232, 252 ] ], "normalized": [] }, { "id": "1496", "type": "(AND other_name other_name other_name other_name)", "text": [ "P-glycoprotein, steroid receptors, p53 and Bcl-2 expression" ], "offsets": [ [ 274, 333 ] ], "normalized": [] }, { "id": "1497", "type": "", "text": [ "P-glycoprotein" ], "offsets": [ [ 274, 288 ] ], "normalized": [] }, { "id": "1498", "type": "", "text": [ "steroid receptors" ], "offsets": [ [ 290, 307 ] ], "normalized": [] }, { "id": "1499", "type": "", "text": [ "p53" ], "offsets": [ [ 309, 312 ] ], "normalized": [] }, { "id": "1500", "type": "", "text": [ "Bcl-2" ], "offsets": [ [ 317, 322 ] ], "normalized": [] }, { "id": "1501", "type": "", "text": [ "expression" ], "offsets": [ [ 323, 333 ] ], "normalized": [] }, { "id": "1502", "type": "lipid", "text": [ "antiestrogens" ], "offsets": [ [ 379, 392 ] ], "normalized": [] }, { "id": "1503", "type": "other_name", "text": [ "cancer therapy" ], "offsets": [ [ 396, 410 ] ], "normalized": [] }, { "id": "1504", "type": "other_name", "text": [ "prevention" ], "offsets": [ [ 415, 425 ] ], "normalized": [] }, { "id": "1505", "type": "other_name", "text": [ "long-term in vivo studies" ], "offsets": [ [ 453, 478 ] ], "normalized": [] } ]

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[ { "id": "1507", "type": "title", "text": [ "The interleukin-5/receptor interaction activates Lyn and Jak2 tyrosine kinases and propagates signals via the Ras-Raf-1-MAP kinase and the Jak-STAT pathways in eosinophils." ], "offsets": [ [ 0, 172 ] ] }, { "id": "1508", "type": "abstract", "text": [ "We have shown that the interaction of interleukin (IL)-5 with the receptor activates Lyn tyrosine kinase within 1 min and Jak2 tyrosine kinase within 1-3 min. IL-5 also stimulates GTP binding to p21ras. The signal is subsequently propagated through the activation of Raf-1, MEK, and MAP kinases as shown by their increased autophosphorylation in vitro and phosphorylation in situ. Jak2 kinase has been shown to phosphorylate STAT nuclear proteins. The activation of STAT nuclear factors was studied by electrophoretic mobility shift assay using a gamma activation site (GAS) probe. We found that IL-5 induces two GAS-binding proteins in eosinophils, one of which is STAT1. We conclude that IL-5 induced signals are propagated through two distinct pathways: (1) Lyn-->Ras-->Raf-1-->MEK-->MAP kinase and (2) Jak2-->STAT1." ], "offsets": [ [ 173, 992 ] ] } ]

[ { "id": "1509", "type": "other_name", "text": [ "interleukin-5/receptor interaction" ], "offsets": [ [ 4, 38 ] ], "normalized": [] }, { "id": "1510", "type": "protein_family_or_group", "text": [ "interleukin-5" ], "offsets": [ [ 4, 17 ] ], "normalized": [] }, { "id": "1511", "type": "(AND protein_family_or_group protein_family_or_group)", "text": [ "Lyn and Jak2 tyrosine kinases" ], "offsets": [ [ 49, 78 ] ], "normalized": [] }, { "id": "1512", "type": "", "text": [ "Lyn" ], "offsets": [ [ 49, 52 ] ], "normalized": [] }, { "id": "1513", "type": "", "text": [ "Jak2" ], "offsets": [ [ 57, 61 ] ], "normalized": [] }, { "id": "1514", "type": "", "text": [ "tyrosine kinases" ], "offsets": [ [ 62, 78 ] ], "normalized": [] }, { "id": "1515", "type": "protein_molecule", "text": [ "Ras-Raf-1-MAP kinase" ], "offsets": [ [ 110, 130 ] ], "normalized": [] }, { "id": "1516", "type": "other_name", "text": [ "Jak-STAT pathways" ], "offsets": [ [ 139, 156 ] ], "normalized": [] }, { "id": "1517", "type": "protein_family_or_group", "text": [ "Jak" ], "offsets": [ [ 57, 60 ] ], "normalized": [] }, { "id": "1518", "type": "protein_family_or_group", "text": [ "-STAT" ], "offsets": [ [ 142, 147 ] ], "normalized": [] }, { "id": "1519", "type": "cell_type", "text": [ "eosinophils" ], "offsets": [ [ 160, 171 ] ], "normalized": [] }, { "id": "1520", "type": "protein_molecule", "text": [ "interleukin (IL)-5" ], "offsets": [ [ 211, 229 ] ], "normalized": [] }, { "id": "1521", "type": "protein_molecule", "text": [ "Lyn tyrosine kinase" ], "offsets": [ [ 258, 277 ] ], "normalized": [] }, { "id": "1522", "type": "protein_molecule", "text": [ "Jak2 tyrosine kinase" ], "offsets": [ [ 295, 315 ] ], "normalized": [] }, { "id": "1523", "type": "protein_molecule", "text": [ "IL-5" ], "offsets": [ [ 332, 336 ] ], "normalized": [] }, { "id": "1524", "type": "other_name", "text": [ "GTP binding" ], "offsets": [ [ 353, 364 ] ], "normalized": [] }, { "id": "1525", "type": "nucleotide", "text": [ "GTP" ], "offsets": [ [ 353, 356 ] ], "normalized": [] }, { "id": "1526", "type": "protein_molecule", "text": [ "p21ras" ], "offsets": [ [ 368, 374 ] ], "normalized": [] }, { "id": "1527", "type": "protein_molecule", "text": [ "Raf-1" ], "offsets": [ [ 440, 445 ] ], "normalized": [] }, { "id": "1528", "type": "protein_family_or_group", "text": [ "MEK" ], "offsets": [ [ 447, 450 ] ], "normalized": [] }, { "id": "1529", "type": "protein_family_or_group", "text": [ "MAP kinases" ], "offsets": [ [ 456, 467 ] ], "normalized": [] }, { "id": "1530", "type": "other_name", "text": [ "autophosphorylation" ], "offsets": [ [ 496, 515 ] ], "normalized": [] }, { "id": "1531", "type": "other_name", "text": [ "phosphorylation" ], "offsets": [ [ 500, 515 ] ], "normalized": [] }, { "id": "1532", "type": "protein_molecule", "text": [ "Jak2 kinase" ], "offsets": [ [ 554, 565 ] ], "normalized": [] }, { "id": "1533", "type": "protein_family_or_group", "text": [ "STAT nuclear proteins" ], "offsets": [ [ 598, 619 ] ], "normalized": [] }, { "id": "1534", "type": "protein_family_or_group", "text": [ "nuclear proteins" ], "offsets": [ [ 603, 619 ] ], "normalized": [] }, { "id": "1535", "type": "protein_family_or_group", "text": [ "STAT nuclear factors" ], "offsets": [ [ 639, 659 ] ], "normalized": [] }, { "id": "1536", "type": "other_name", "text": [ "electrophoretic mobility shift assay" ], "offsets": [ [ 675, 711 ] ], "normalized": [] }, { "id": "1537", "type": "other_name", "text": [ "gamma activation site (GAS) probe" ], "offsets": [ [ 720, 753 ] ], "normalized": [] }, { "id": "1538", "type": "DNA_domain_or_region", "text": [ "gamma activation site" ], "offsets": [ [ 720, 741 ] ], "normalized": [] }, { "id": "1539", "type": "DNA_domain_or_region", "text": [ "GAS" ], "offsets": [ [ 743, 746 ] ], "normalized": [] }, { "id": "1540", "type": "protein_molecule", "text": [ "IL-5" ], "offsets": [ [ 769, 773 ] ], "normalized": [] }, { "id": "1541", "type": "protein_family_or_group", "text": [ "GAS-binding proteins" ], "offsets": [ [ 786, 806 ] ], "normalized": [] }, { "id": "1542", "type": "cell_type", "text": [ "eosinophils" ], "offsets": [ [ 810, 821 ] ], "normalized": [] }, { "id": "1543", "type": "protein_molecule", "text": [ "STAT1" ], "offsets": [ [ 839, 844 ] ], "normalized": [] }, { "id": "1544", "type": "other_name", "text": [ "IL-5 induced signals" ], "offsets": [ [ 863, 883 ] ], "normalized": [] }, { "id": "1545", "type": "protein_molecule", "text": [ "IL-5" ], "offsets": [ [ 863, 867 ] ], "normalized": [] }, { "id": "1546", "type": "protein_family_or_group", "text": [ "Lyn" ], "offsets": [ [ 934, 937 ] ], "normalized": [] }, { "id": "1547", "type": "protein_family_or_group", "text": [ "Ras" ], "offsets": [ [ 940, 943 ] ], "normalized": [] }, { "id": "1548", "type": "protein_molecule", "text": [ "Raf-1" ], "offsets": [ [ 946, 951 ] ], "normalized": [] }, { "id": "1549", "type": "protein_family_or_group", "text": [ "MEK" ], "offsets": [ [ 954, 957 ] ], "normalized": [] }, { "id": "1550", "type": "protein_family_or_group", "text": [ "MAP kinase" ], "offsets": [ [ 960, 970 ] ], "normalized": [] }, { "id": "1551", "type": "protein_molecule", "text": [ "Jak2" ], "offsets": [ [ 979, 983 ] ], "normalized": [] }, { "id": "1552", "type": "protein_molecule", "text": [ "STAT1" ], "offsets": [ [ 986, 991 ] ], "normalized": [] } ]

[]

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[ { "id": "1554", "type": "title", "text": [ "The retinoblastoma gene product negatively regulates transcriptional activation mediated by the human cytomegalovirus IE2 protein." ], "offsets": [ [ 0, 130 ] ] }, { "id": "1555", "type": "abstract", "text": [ "The IE2 gene product of human cytomegalovirus (HCMV) is one of a few viral regulatory proteins expressed immediately upon infection of the host cell. It is a potent transcriptional activator of many viral and cellular promoters. We found that the retinoblastoma susceptibility gene product (Rb) dramatically suppressed this IE2 transactivation of various promoters. However, unlike another tumor suppressor protein, p53, Rb did not have any significant effect on basal levels of transcription, suggesting that Rb specifically interacts with IE2 rather than other cellular factors involved in the general transcription machinery. We found by protein-affinity chromatography that Rb in nuclear extracts or produced by in vitro translation directly bound to IE2. Our results suggest that Rb may regulate the life cycle of HCMV, which is endemic in the human population. Furthermore, these data may provide new insights into the slow rate of HCMV DNA replication in cells and the possible involvement of HCMV in tumorigenesis." ], "offsets": [ [ 131, 1153 ] ] } ]

[ { "id": "1556", "type": "protein_molecule", "text": [ "retinoblastoma gene product" ], "offsets": [ [ 4, 31 ] ], "normalized": [] }, { "id": "1557", "type": "protein_N/A", "text": [ "transcriptional activation" ], "offsets": [ [ 53, 79 ] ], "normalized": [] }, { "id": "1558", "type": "protein_molecule", "text": [ "human cytomegalovirus IE2 protein" ], "offsets": [ [ 96, 129 ] ], "normalized": [] }, { "id": "1559", "type": "virus", "text": [ "human cytomegalovirus" ], "offsets": [ [ 96, 117 ] ], "normalized": [] }, { "id": "1560", "type": "protein_molecule", "text": [ "IE2 gene product" ], "offsets": [ [ 135, 151 ] ], "normalized": [] }, { "id": "1561", "type": "virus", "text": [ "human cytomegalovirus" ], "offsets": [ [ 155, 176 ] ], "normalized": [] }, { "id": "1562", "type": "virus", "text": [ "HCMV" ], "offsets": [ [ 178, 182 ] ], "normalized": [] }, { "id": "1563", "type": "protein_family_or_group", "text": [ "viral regulatory proteins" ], "offsets": [ [ 200, 225 ] ], "normalized": [] }, { "id": "1564", "type": "other_name", "text": [ "infection" ], "offsets": [ [ 253, 262 ] ], "normalized": [] }, { "id": "1565", "type": "cell_type", "text": [ "host cell" ], "offsets": [ [ 270, 279 ] ], "normalized": [] }, { "id": "1566", "type": "protein_family_or_group", "text": [ "transcriptional activator" ], "offsets": [ [ 296, 321 ] ], "normalized": [] }, { "id": "1567", "type": "(AND DNA_family_or_group DNA_family_or_group)", "text": [ "viral and cellular promoters" ], "offsets": [ [ 330, 358 ] ], "normalized": [] }, { "id": "1568", "type": "", "text": [ "viral" ], "offsets": [ [ 330, 335 ] ], "normalized": [] }, { "id": "1569", "type": "", "text": [ "cellular" ], "offsets": [ [ 340, 348 ] ], "normalized": [] }, { "id": "1570", "type": "", "text": [ "promoters" ], "offsets": [ [ 349, 358 ] ], "normalized": [] }, { "id": "1571", "type": "protein_molecule", "text": [ "retinoblastoma susceptibility gene product" ], "offsets": [ [ 378, 420 ] ], "normalized": [] }, { "id": "1572", "type": "protein_molecule", "text": [ "Rb" ], "offsets": [ [ 422, 424 ] ], "normalized": [] }, { "id": "1573", "type": "other_name", "text": [ "IE2 transactivation" ], "offsets": [ [ 455, 474 ] ], "normalized": [] }, { "id": "1574", "type": "protein_molecule", "text": [ "IE2" ], "offsets": [ [ 455, 458 ] ], "normalized": [] }, { "id": "1575", "type": "DNA_family_or_group", "text": [ "various promoters" ], "offsets": [ [ 478, 495 ] ], "normalized": [] }, { "id": "1576", "type": "protein_family_or_group", "text": [ "tumor suppressor protein" ], "offsets": [ [ 521, 545 ] ], "normalized": [] }, { "id": "1577", "type": "protein_molecule", "text": [ "p53" ], "offsets": [ [ 547, 550 ] ], "normalized": [] }, { "id": "1578", "type": "protein_molecule", "text": [ "Rb" ], "offsets": [ [ 552, 554 ] ], "normalized": [] }, { "id": "1579", "type": "other_name", "text": [ "basal levels" ], "offsets": [ [ 594, 606 ] ], "normalized": [] }, { "id": "1580", "type": "other_name", "text": [ "transcription" ], "offsets": [ [ 610, 623 ] ], "normalized": [] }, { "id": "1581", "type": "protein_molecule", "text": [ "Rb" ], "offsets": [ [ 641, 643 ] ], "normalized": [] }, { "id": "1582", "type": "protein_molecule", "text": [ "IE2" ], "offsets": [ [ 672, 675 ] ], "normalized": [] }, { "id": "1583", "type": "protein_family_or_group", "text": [ "cellular factors" ], "offsets": [ [ 694, 710 ] ], "normalized": [] }, { "id": "1584", "type": "other_name", "text": [ "transcription machinery" ], "offsets": [ [ 735, 758 ] ], "normalized": [] }, { "id": "1585", "type": "other_name", "text": [ "protein-affinity chromatography" ], "offsets": [ [ 772, 803 ] ], "normalized": [] }, { "id": "1586", "type": "protein_molecule", "text": [ "Rb" ], "offsets": [ [ 809, 811 ] ], "normalized": [] }, { "id": "1587", "type": "cell_component", "text": [ "nuclear extracts" ], "offsets": [ [ 815, 831 ] ], "normalized": [] }, { "id": "1588", "type": "protein_molecule", "text": [ "IE2" ], "offsets": [ [ 886, 889 ] ], "normalized": [] }, { "id": "1589", "type": "protein_molecule", "text": [ "Rb" ], "offsets": [ [ 916, 918 ] ], "normalized": [] }, { "id": "1590", "type": "virus", "text": [ "HCMV" ], "offsets": [ [ 950, 954 ] ], "normalized": [] }, { "id": "1591", "type": "multi_cell", "text": [ "human population" ], "offsets": [ [ 980, 996 ] ], "normalized": [] }, { "id": "1592", "type": "other_name", "text": [ "HCMV DNA replication" ], "offsets": [ [ 1069, 1089 ] ], "normalized": [] }, { "id": "1593", "type": "virus", "text": [ "HCMV" ], "offsets": [ [ 1069, 1073 ] ], "normalized": [] }, { "id": "1594", "type": "virus", "text": [ "HCMV" ], "offsets": [ [ 1131, 1135 ] ], "normalized": [] }, { "id": "1595", "type": "other_name", "text": [ "tumorigenesis" ], "offsets": [ [ 1139, 1152 ] ], "normalized": [] } ]

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[ { "id": "1597", "type": "title", "text": [ "Expression of the nucleoside diphosphate kinase in human skin cancers: an immunohistochemical study." ], "offsets": [ [ 0, 100 ] ] }, { "id": "1598", "type": "abstract", "text": [ "Expression of nucleoside diphosphate(NDP) kinase, which is homologous to the nm23 gene product in a variety of species, has been found to be inversely associated with metastatic potential. However, the relationship remains controversial according to the tumor cell types and experimental system, with conflicting results from different research groups. In order to determine whether NDP kinase expression serves as a marker for metastatic potential in human skin cancer, we assessed the levels of NDP kinase expression in 9 keratoacanthomas (KAs), 26 squamous cell carcinomas (SCCs), and 25 basal cell carcinomas (BCCs) using immunohistochemistry. The expression of NDP kinase was intense in KA and SCC compared with BCC. However, the difference of NDP kinase expression between KA and SCC was not statistically significant. And there was no statistically significant difference in NDP kinase expression between SCC with metastasis and SCC without metastasis. Our results contradict the hypothesis concerning the possible role of nm23 gene as a metastatic suppressor gene in human skin cancer. The mechanism of overexpression in various tumor cell types and its biological significance in cutaneous carcinogenesis remain to be determined." ], "offsets": [ [ 101, 1339 ] ] } ]

[ { "id": "1599", "type": "protein_molecule", "text": [ "nucleoside diphosphate kinase" ], "offsets": [ [ 18, 47 ] ], "normalized": [] }, { "id": "1600", "type": "other_name", "text": [ "human skin cancers" ], "offsets": [ [ 51, 69 ] ], "normalized": [] }, { "id": "1601", "type": "other_name", "text": [ "immunohistochemical study" ], "offsets": [ [ 74, 99 ] ], "normalized": [] }, { "id": "1602", "type": "protein_molecule", "text": [ "nucleoside diphosphate(NDP) kinase" ], "offsets": [ [ 115, 149 ] ], "normalized": [] }, { "id": "1603", "type": "protein_molecule", "text": [ "nm23 gene product" ], "offsets": [ [ 178, 195 ] ], "normalized": [] }, { "id": "1604", "type": "DNA_domain_or_region", "text": [ "nm23 gene" ], "offsets": [ [ 178, 187 ] ], "normalized": [] }, { "id": "1605", "type": "other_name", "text": [ "metastatic potential" ], "offsets": [ [ 268, 288 ] ], "normalized": [] }, { "id": "1606", "type": "cell_type", "text": [ "tumor cell types" ], "offsets": [ [ 355, 371 ] ], "normalized": [] }, { "id": "1607", "type": "other_name", "text": [ "experimental system" ], "offsets": [ [ 376, 395 ] ], "normalized": [] }, { "id": "1608", "type": "other_name", "text": [ "NDP kinase expression" ], "offsets": [ [ 484, 505 ] ], "normalized": [] }, { "id": "1609", "type": "protein_molecule", "text": [ "NDP kinase" ], "offsets": [ [ 484, 494 ] ], "normalized": [] }, { "id": "1610", "type": "other_name", "text": [ "metastatic potential" ], "offsets": [ [ 529, 549 ] ], "normalized": [] }, { "id": "1611", "type": "other_name", "text": [ "human skin cancer" ], "offsets": [ [ 553, 570 ] ], "normalized": [] }, { "id": "1612", "type": "other_name", "text": [ "NDP kinase expression" ], "offsets": [ [ 598, 619 ] ], "normalized": [] }, { "id": "1613", "type": "protein_molecule", "text": [ "NDP kinase" ], "offsets": [ [ 598, 608 ] ], "normalized": [] }, { "id": "1614", "type": "other_name", "text": [ "keratoacanthomas" ], "offsets": [ [ 625, 641 ] ], "normalized": [] }, { "id": "1615", "type": "other_name", "text": [ "KAs" ], "offsets": [ [ 643, 646 ] ], "normalized": [] }, { "id": "1616", "type": "other_name", "text": [ "squamous cell carcinomas" ], "offsets": [ [ 652, 676 ] ], "normalized": [] }, { "id": "1617", "type": "other_name", "text": [ "SCCs" ], "offsets": [ [ 678, 682 ] ], "normalized": [] }, { "id": "1618", "type": "other_name", "text": [ "basal cell carcinomas" ], "offsets": [ [ 692, 713 ] ], "normalized": [] }, { "id": "1619", "type": "other_name", "text": [ "BCCs" ], "offsets": [ [ 715, 719 ] ], "normalized": [] }, { "id": "1620", "type": "other_name", "text": [ "immunohistochemistry" ], "offsets": [ [ 727, 747 ] ], "normalized": [] }, { "id": "1621", "type": "protein_molecule", "text": [ "NDP kinase" ], "offsets": [ [ 767, 777 ] ], "normalized": [] }, { "id": "1622", "type": "other_name", "text": [ "KA" ], "offsets": [ [ 793, 795 ] ], "normalized": [] }, { "id": "1623", "type": "other_name", "text": [ "SCC" ], "offsets": [ [ 800, 803 ] ], "normalized": [] }, { "id": "1624", "type": "other_name", "text": [ "BCC" ], "offsets": [ [ 818, 821 ] ], "normalized": [] }, { "id": "1625", "type": "other_name", "text": [ "NDP kinase expression" ], "offsets": [ [ 850, 871 ] ], "normalized": [] }, { "id": "1626", "type": "protein_molecule", "text": [ "NDP kinase" ], "offsets": [ [ 850, 860 ] ], "normalized": [] }, { "id": "1627", "type": "other_name", "text": [ "KA" ], "offsets": [ [ 880, 882 ] ], "normalized": [] }, { "id": "1628", "type": "other_name", "text": [ "SCC" ], "offsets": [ [ 887, 890 ] ], "normalized": [] }, { "id": "1629", "type": "other_name", "text": [ "NDP kinase expression" ], "offsets": [ [ 983, 1004 ] ], "normalized": [] }, { "id": "1630", "type": "protein_molecule", "text": [ "NDP kinase" ], "offsets": [ [ 983, 993 ] ], "normalized": [] }, { "id": "1631", "type": "other_name", "text": [ "SCC" ], "offsets": [ [ 1013, 1016 ] ], "normalized": [] }, { "id": "1632", "type": "other_name", "text": [ "metastasis" ], "offsets": [ [ 1022, 1032 ] ], "normalized": [] }, { "id": "1633", "type": "other_name", "text": [ "SCC" ], "offsets": [ [ 1037, 1040 ] ], "normalized": [] }, { "id": "1634", "type": "other_name", "text": [ "metastasis" ], "offsets": [ [ 1049, 1059 ] ], "normalized": [] }, { "id": "1635", "type": "DNA_domain_or_region", "text": [ "nm23 gene" ], "offsets": [ [ 1131, 1140 ] ], "normalized": [] }, { "id": "1636", "type": "other_name", "text": [ "human skin cancer" ], "offsets": [ [ 1176, 1193 ] ], "normalized": [] }, { "id": "1637", "type": "other_name", "text": [ "overexpression" ], "offsets": [ [ 1212, 1226 ] ], "normalized": [] }, { "id": "1638", "type": "cell_type", "text": [ "tumor cell types" ], "offsets": [ [ 1238, 1254 ] ], "normalized": [] }, { "id": "1639", "type": "other_name", "text": [ "biological significance" ], "offsets": [ [ 1263, 1286 ] ], "normalized": [] }, { "id": "1640", "type": "other_name", "text": [ "cutaneous carcinogenesis" ], "offsets": [ [ 1290, 1314 ] ], "normalized": [] } ]

[]

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[ { "id": "1642", "type": "title", "text": [ "RB and a novel E2F-1 binding protein in MHC class II deficient B-cell lines and normal IFN-gamma induction of the class IL transactivator CIITA in class II non-inducible RB-defective tumor lines." ], "offsets": [ [ 0, 195 ] ] }, { "id": "1643", "type": "abstract", "text": [ "The major histocompatibility (MHC) class II genes encode cell surface proteins that bind antigenic peptide for presentation to T-cells. The class II proteins are expressed constitutively on B-cells and EBV-transformed B-cells, and are inducible by IFN-gamma on a wide variety of cell types. Retinoblastoma protein (RB) is a tumor suppressor and functions as a transcriptional repressor by binding and inactivating the transactivator E2F-I. RB-defective tumor lines are non-inducible for MHC class II by IFN-gamma, or very weakly inducible, but transfection of 2 different lines with RB expression vectors re-establishes or substantially enhances class II inducibility. Therefore, we examined the RB status of a series of B-cell mutants that are defective in class II expression, generated either in vitro or derived from Bare Lymphocyte Syndrome (BLS) patients. Nuclear matrix-bound RB was detectable in all cases, indicating that loss of RB is not responsible for decreased class II expression in these lines. A second E2F-I binding protein, most likely DP-I, was also apparently normal in both class II-positive and -negative B-cell lines. We also examined the IFN-gamma induction of CIITA in RB-defective lines. CIITA is a class II gene transactivator known to be defective in one form of BLS and to be required for the induction of MHC class II by IFN-gamma. CIITA mRNA is normally inducible by IFN-gamma in class II non-inducible, RB-defective lines, and in one line, re-expression of RB has no effect on CIITA mRNA induction levels. Thus, the block in MHC class II inducibility in RB-defective cells is not due to a block in CIITA inducibility." ], "offsets": [ [ 196, 1846 ] ] } ]

[ { "id": "1644", "type": "protein_molecule", "text": [ "RB" ], "offsets": [ [ 0, 2 ] ], "normalized": [] }, { "id": "1645", "type": "protein_family_or_group", "text": [ "E2F-1 binding protein" ], "offsets": [ [ 15, 36 ] ], "normalized": [] }, { "id": "1646", "type": "cell_line", "text": [ "MHC class II deficient B-cell lines" ], "offsets": [ [ 40, 75 ] ], "normalized": [] }, { "id": "1647", "type": "other_name", "text": [ "IFN-gamma induction" ], "offsets": [ [ 87, 106 ] ], "normalized": [] }, { "id": "1648", "type": "protein_molecule", "text": [ "IFN-gamma" ], "offsets": [ [ 87, 96 ] ], "normalized": [] }, { "id": "1649", "type": "DNA_domain_or_region", "text": [ "class IL transactivator" ], "offsets": [ [ 114, 137 ] ], "normalized": [] }, { "id": "1650", "type": "DNA_domain_or_region", "text": [ "CIITA" ], "offsets": [ [ 138, 143 ] ], "normalized": [] }, { "id": "1651", "type": "cell_line", "text": [ "class II non-inducible RB-defective tumor lines" ], "offsets": [ [ 147, 194 ] ], "normalized": [] }, { "id": "1652", "type": "protein_molecule", "text": [ "RB" ], "offsets": [ [ 170, 172 ] ], "normalized": [] }, { "id": "1653", "type": "DNA_family_or_group", "text": [ "major histocompatibility (MHC) class II genes" ], "offsets": [ [ 200, 245 ] ], "normalized": [] }, { "id": "1654", "type": "protein_family_or_group", "text": [ "cell surface proteins" ], "offsets": [ [ 253, 274 ] ], "normalized": [] }, { "id": "1655", "type": "peptide", "text": [ "antigenic peptide" ], "offsets": [ [ 285, 302 ] ], "normalized": [] }, { "id": "1656", "type": "cell_type", "text": [ "T-cells" ], "offsets": [ [ 323, 330 ] ], "normalized": [] }, { "id": "1657", "type": "protein_family_or_group", "text": [ "class II proteins" ], "offsets": [ [ 336, 353 ] ], "normalized": [] }, { "id": "1658", "type": "cell_type", "text": [ "B-cells" ], "offsets": [ [ 386, 393 ] ], "normalized": [] }, { "id": "1659", "type": "cell_line", "text": [ "EBV-transformed B-cells," ], "offsets": [ [ 398, 422 ] ], "normalized": [] }, { "id": "1660", "type": "cell_type", "text": [ "B-cells" ], "offsets": [ [ 414, 421 ] ], "normalized": [] }, { "id": "1661", "type": "protein_molecule", "text": [ "IFN-gamma" ], "offsets": [ [ 444, 453 ] ], "normalized": [] }, { "id": "1662", "type": "cell_type", "text": [ "cell types" ], "offsets": [ [ 475, 485 ] ], "normalized": [] }, { "id": "1663", "type": "protein_family_or_group", "text": [ "Retinoblastoma protein" ], "offsets": [ [ 487, 509 ] ], "normalized": [] }, { "id": "1664", "type": "protein_molecule", "text": [ "RB" ], "offsets": [ [ 511, 513 ] ], "normalized": [] }, { "id": "1665", "type": "other_name", "text": [ "tumor suppressor" ], "offsets": [ [ 520, 536 ] ], "normalized": [] }, { "id": "1666", "type": "protein_family_or_group", "text": [ "transcriptional repressor" ], "offsets": [ [ 556, 581 ] ], "normalized": [] }, { "id": "1667", "type": "DNA_domain_or_region", "text": [ "transactivator E2F-I" ], "offsets": [ [ 614, 634 ] ], "normalized": [] }, { "id": "1668", "type": "cell_line", "text": [ "RB-defective tumor lines" ], "offsets": [ [ 636, 660 ] ], "normalized": [] }, { "id": "1669", "type": "protein_molecule", "text": [ "RB" ], "offsets": [ [ 636, 638 ] ], "normalized": [] }, { "id": "1670", "type": "protein_family_or_group", "text": [ "MHC class II" ], "offsets": [ [ 683, 695 ] ], "normalized": [] }, { "id": "1671", "type": "protein_molecule", "text": [ "IFN-gamma" ], "offsets": [ [ 699, 708 ] ], "normalized": [] }, { "id": "1672", "type": "DNA_family_or_group", "text": [ "RB expression vectors" ], "offsets": [ [ 779, 800 ] ], "normalized": [] }, { "id": "1673", "type": "protein_molecule", "text": [ "RB" ], "offsets": [ [ 779, 781 ] ], "normalized": [] }, { "id": "1674", "type": "other_name", "text": [ "class II inducibility" ], "offsets": [ [ 842, 863 ] ], "normalized": [] }, { "id": "1675", "type": "protein_molecule", "text": [ "RB" ], "offsets": [ [ 892, 894 ] ], "normalized": [] }, { "id": "1676", "type": "protein_molecule", "text": [ "RB" ], "offsets": [ [ 1079, 1081 ] ], "normalized": [] }, { "id": "1677", "type": "protein_molecule", "text": [ "RB" ], "offsets": [ [ 1135, 1137 ] ], "normalized": [] }, { "id": "1678", "type": "other_name", "text": [ "IFN-gamma induction" ], "offsets": [ [ 1359, 1378 ] ], "normalized": [] }, { "id": "1679", "type": "protein_molecule", "text": [ "IFN-gamma" ], "offsets": [ [ 1359, 1368 ] ], "normalized": [] }, { "id": "1680", "type": "DNA_domain_or_region", "text": [ "CIITA" ], "offsets": [ [ 1382, 1387 ] ], "normalized": [] }, { "id": "1681", "type": "protein_molecule", "text": [ "RB" ], "offsets": [ [ 1391, 1393 ] ], "normalized": [] }, { "id": "1682", "type": "DNA_domain_or_region", "text": [ "CIITA" ], "offsets": [ [ 1411, 1416 ] ], "normalized": [] }, { "id": "1683", "type": "DNA_family_or_group", "text": [ "class II gene transactivator" ], "offsets": [ [ 1422, 1450 ] ], "normalized": [] }, { "id": "1684", "type": "other_name", "text": [ "BLS" ], "offsets": [ [ 1488, 1491 ] ], "normalized": [] }, { "id": "1685", "type": "protein_family_or_group", "text": [ "MHC class II" ], "offsets": [ [ 1532, 1544 ] ], "normalized": [] }, { "id": "1686", "type": "protein_molecule", "text": [ "IFN-gamma" ], "offsets": [ [ 1548, 1557 ] ], "normalized": [] }, { "id": "1687", "type": "RNA_family_or_group", "text": [ "CIITA mRNA" ], "offsets": [ [ 1559, 1569 ] ], "normalized": [] }, { "id": "1688", "type": "DNA_domain_or_region", "text": [ "CIITA" ], "offsets": [ [ 1559, 1564 ] ], "normalized": [] }, { "id": "1689", "type": "protein_molecule", "text": [ "IFN-gamma" ], "offsets": [ [ 1595, 1604 ] ], "normalized": [] }, { "id": "1690", "type": "cell_line", "text": [ "class II non-inducible, RB-defective lines" ], "offsets": [ [ 1608, 1650 ] ], "normalized": [] }, { "id": "1691", "type": "protein_molecule", "text": [ "RB" ], "offsets": [ [ 1632, 1634 ] ], "normalized": [] }, { "id": "1692", "type": "other_name", "text": [ "re-expression" ], "offsets": [ [ 1669, 1682 ] ], "normalized": [] }, { "id": "1693", "type": "protein_molecule", "text": [ "RB" ], "offsets": [ [ 1686, 1688 ] ], "normalized": [] }, { "id": "1694", "type": "other_name", "text": [ "CIITA mRNA induction levels" ], "offsets": [ [ 1706, 1733 ] ], "normalized": [] }, { "id": "1695", "type": "RNA_family_or_group", "text": [ "CIITA mRNA" ], "offsets": [ [ 1706, 1716 ] ], "normalized": [] }, { "id": "1696", "type": "DNA_domain_or_region", "text": [ "CIITA" ], "offsets": [ [ 1706, 1711 ] ], "normalized": [] }, { "id": "1697", "type": "other_name", "text": [ "MHC class II inducibility" ], "offsets": [ [ 1754, 1779 ] ], "normalized": [] }, { "id": "1698", "type": "other_name", "text": [ "class II inducibility" ], "offsets": [ [ 1758, 1779 ] ], "normalized": [] }, { "id": "1699", "type": "cell_line", "text": [ "RB-defective cells" ], "offsets": [ [ 1783, 1801 ] ], "normalized": [] }, { "id": "1700", "type": "protein_molecule", "text": [ "RB" ], "offsets": [ [ 1783, 1785 ] ], "normalized": [] }, { "id": "1701", "type": "other_name", "text": [ "CIITA inducibility" ], "offsets": [ [ 1827, 1845 ] ], "normalized": [] }, { "id": "1702", "type": "DNA_domain_or_region", "text": [ "CIITA" ], "offsets": [ [ 1827, 1832 ] ], "normalized": [] } ]

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[ { "id": "1704", "type": "title", "text": [ "Interleukin 12 induces tyrosine phosphorylation and activation of STAT4 in human lymphocytes." ], "offsets": [ [ 0, 93 ] ] }, { "id": "1705", "type": "abstract", "text": [ "Interleukin 12 (IL-12) is an important immunoregulatory cytokine whose receptor is a member of the hematopoietin receptor superfamily. We have recently demonstrated that stimulation of human T and natural killer cells with IL-12 induces tyrosine phosphorylation of the Janus family tyrosine kinase JAK2 and Tyk2, implicating these kinases in the immediate biochemical response to IL-12. Recently, transcription factors known as STATs (signal transducers and activators of transcription) have been shown to be tyrosine phosphorylated and activated in response to a number of cytokines that bind hematopoietin receptors and activate JAK kinases. In this report we demonstrate that IL-12 induces tyrosine phosphorylation of a recently identified STAT family member, STAT4, and show that STAT4 expression is regulated by T-cell activation. Furthermore, we show that IL-12 stimulates formation of a DNA-binding complex that recognizes a DNA sequence previously shown to bind STAT proteins and that this complex contains STAT4. These data, and the recent demonstration of JAK phosphorylation by IL-12, identify a rapid signal-transduction pathway likely to mediate IL-12-induced gene expression." ], "offsets": [ [ 94, 1283 ] ] } ]

[ { "id": "1706", "type": "protein_molecule", "text": [ "Interleukin 12" ], "offsets": [ [ 0, 14 ] ], "normalized": [] }, { "id": "1707", "type": "other_name", "text": [ "tyrosine phosphorylation" ], "offsets": [ [ 23, 47 ] ], "normalized": [] }, { "id": "1708", "type": "amino_acid_monomer", "text": [ "tyrosine" ], "offsets": [ [ 23, 31 ] ], "normalized": [] }, { "id": "1709", "type": "protein_molecule", "text": [ "STAT4" ], "offsets": [ [ 66, 71 ] ], "normalized": [] }, { "id": "1710", "type": "cell_type", "text": [ "human lymphocytes" ], "offsets": [ [ 75, 92 ] ], "normalized": [] }, { "id": "1711", "type": "protein_molecule", "text": [ "Interleukin 12" ], "offsets": [ [ 94, 108 ] ], "normalized": [] }, { "id": "1712", "type": "protein_molecule", "text": [ "IL-12" ], "offsets": [ [ 110, 115 ] ], "normalized": [] }, { "id": "1713", "type": "protein_family_or_group", "text": [ "immunoregulatory cytokine" ], "offsets": [ [ 133, 158 ] ], "normalized": [] }, { "id": "1714", "type": "protein_family_or_group", "text": [ "hematopoietin receptor superfamily" ], "offsets": [ [ 193, 227 ] ], "normalized": [] }, { "id": "1715", "type": "(AND cell_type cell_type)", "text": [ "human T and natural killer cells" ], "offsets": [ [ 279, 311 ] ], "normalized": [] }, { "id": "1716", "type": "", "text": [ "human" ], "offsets": [ [ 279, 284 ] ], "normalized": [] }, { "id": "1717", "type": "", "text": [ "T" ], "offsets": [ [ 285, 286 ] ], "normalized": [] }, { "id": "1718", "type": "", "text": [ "natural killer" ], "offsets": [ [ 291, 305 ] ], "normalized": [] }, { "id": "1719", "type": "", "text": [ "cells" ], "offsets": [ [ 306, 311 ] ], "normalized": [] }, { "id": "1720", "type": "protein_molecule", "text": [ "IL-12" ], "offsets": [ [ 317, 322 ] ], "normalized": [] }, { "id": "1721", "type": "other_name", "text": [ "tyrosine phosphorylation" ], "offsets": [ [ 331, 355 ] ], "normalized": [] }, { "id": "1722", "type": "amino_acid_monomer", "text": [ "tyrosine" ], "offsets": [ [ 331, 339 ] ], "normalized": [] }, { "id": "1723", "type": "protein_family_or_group", "text": [ "Janus family tyrosine kinase" ], "offsets": [ [ 363, 391 ] ], "normalized": [] }, { "id": "1724", "type": "amino_acid_monomer", "text": [ "tyrosine" ], "offsets": [ [ 376, 384 ] ], "normalized": [] }, { "id": "1725", "type": "protein_molecule", "text": [ "JAK2" ], "offsets": [ [ 392, 396 ] ], "normalized": [] }, { "id": "1726", "type": "protein_molecule", "text": [ "Tyk2" ], "offsets": [ [ 401, 405 ] ], "normalized": [] }, { "id": "1727", "type": "protein_family_or_group", "text": [ "kinases" ], "offsets": [ [ 425, 432 ] ], "normalized": [] }, { "id": "1728", "type": "protein_molecule", "text": [ "IL-12" ], "offsets": [ [ 474, 479 ] ], "normalized": [] }, { "id": "1729", "type": "protein_family_or_group", "text": [ "transcription factors" ], "offsets": [ [ 491, 512 ] ], "normalized": [] }, { "id": "1730", "type": "protein_family_or_group", "text": [ "STATs" ], "offsets": [ [ 522, 527 ] ], "normalized": [] }, { "id": "1731", "type": "protein_family_or_group", "text": [ "signal transducers and activators of transcription" ], "offsets": [ [ 529, 579 ] ], "normalized": [] }, { "id": "1732", "type": "other_name", "text": [ "tyrosine phosphorylated" ], "offsets": [ [ 603, 626 ] ], "normalized": [] }, { "id": "1733", "type": "amino_acid_monomer", "text": [ "tyrosine" ], "offsets": [ [ 603, 611 ] ], "normalized": [] }, { "id": "1734", "type": "protein_family_or_group", "text": [ "cytokines" ], "offsets": [ [ 668, 677 ] ], "normalized": [] }, { "id": "1735", "type": "protein_family_or_group", "text": [ "hematopoietin receptors" ], "offsets": [ [ 688, 711 ] ], "normalized": [] }, { "id": "1736", "type": "protein_family_or_group", "text": [ "JAK kinases" ], "offsets": [ [ 725, 736 ] ], "normalized": [] }, { "id": "1737", "type": "protein_molecule", "text": [ "IL-12" ], "offsets": [ [ 773, 778 ] ], "normalized": [] }, { "id": "1738", "type": "other_name", "text": [ "tyrosine phosphorylation" ], "offsets": [ [ 787, 811 ] ], "normalized": [] }, { "id": "1739", "type": "amino_acid_monomer", "text": [ "tyrosine" ], "offsets": [ [ 787, 795 ] ], "normalized": [] }, { "id": "1740", "type": "protein_family_or_group", "text": [ "STAT family member" ], "offsets": [ [ 837, 855 ] ], "normalized": [] }, { "id": "1741", "type": "protein_molecule", "text": [ "STAT4" ], "offsets": [ [ 857, 862 ] ], "normalized": [] }, { "id": "1742", "type": "other_name", "text": [ "STAT4 expression" ], "offsets": [ [ 878, 894 ] ], "normalized": [] }, { "id": "1743", "type": "protein_molecule", "text": [ "STAT4" ], "offsets": [ [ 878, 883 ] ], "normalized": [] }, { "id": "1744", "type": "other_name", "text": [ "T-cell activation" ], "offsets": [ [ 911, 928 ] ], "normalized": [] }, { "id": "1745", "type": "protein_molecule", "text": [ "IL-12" ], "offsets": [ [ 956, 961 ] ], "normalized": [] }, { "id": "1746", "type": "protein_complex", "text": [ "DNA-binding complex" ], "offsets": [ [ 988, 1007 ] ], "normalized": [] }, { "id": "1747", "type": "protein_family_or_group", "text": [ "STAT proteins" ], "offsets": [ [ 1064, 1077 ] ], "normalized": [] }, { "id": "1748", "type": "protein_molecule", "text": [ "STAT4" ], "offsets": [ [ 1109, 1114 ] ], "normalized": [] }, { "id": "1749", "type": "other_name", "text": [ "JAK phosphorylation" ], "offsets": [ [ 1160, 1179 ] ], "normalized": [] }, { "id": "1750", "type": "protein_family_or_group", "text": [ "JAK" ], "offsets": [ [ 1160, 1163 ] ], "normalized": [] }, { "id": "1751", "type": "protein_molecule", "text": [ "IL-12" ], "offsets": [ [ 1183, 1188 ] ], "normalized": [] }, { "id": "1752", "type": "other_name", "text": [ "signal-transduction pathway" ], "offsets": [ [ 1207, 1234 ] ], "normalized": [] }, { "id": "1753", "type": "other_name", "text": [ "IL-12-induced gene expression" ], "offsets": [ [ 1253, 1282 ] ], "normalized": [] }, { "id": "1754", "type": "protein_molecule", "text": [ "IL-12" ], "offsets": [ [ 1253, 1258 ] ], "normalized": [] } ]

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[]

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[ { "id": "1756", "type": "title", "text": [ "Temperature-induced down-regulation of the glucocorticoid receptor in peripheral blood mononuclear leucocyte in patients with sepsis or septic shock." ], "offsets": [ [ 0, 149 ] ] }, { "id": "1757", "type": "abstract", "text": [ "OBJECTIVE: Activation of the hypothalamic-pituitary-adrenal axis is of vital importance during critical illness. We have studied the adaptive mechanisms which occur at the level of the glucocorticoid receptor in glucocorticoid target tissues in patients with sepsis or septic shock. DESIGN: The effects of hypercortisolaemia, hyperthermia and cellular composition on number of glucocorticoid receptors per cell and their affinity were evaluated, both in vitro and in vivo, in peripheral blood mononuclear leucocytes of control subjects and in patients with sepsis or septic shock. SUBJECTS: Fifteen patients (age 25-79) with sepsis or septic shock who were admitted to an intensive care unit were studied. The control group consisted of 24 healthy laboratory employees. MEASUREMENTS: The binding capacity and affinity of the glucocorticoid receptors were measured and compared to clinical data and the plasma cortisol concentrations. RESULTS: Hypercortisolaemia, in vitro, resulted in a decreased affinity and a decreased binding capacity of the glucocorticoid receptor. In vitro, hyperthermia as well as variations in the cellular composition did not influence the glucocorticoid receptor. In vivo, there was no change in the number of receptors per cell in patients with sepsis or septic shock as compared to healthy controls. However, a decreased affinity of the glucocorticoid receptor was observed. There was a weak but significant negative correlation between body temperature and the number of glucocorticoid receptors in the patient group. There was no relation between circulating cortisol concentrations and glucocorticoid receptor affinity and number. CONCLUSIONS: There is no obvious regulation of the number of glucocorticoid receptors by plasma cortisol concentrations in vivo. The decreased affinity of the glucocorticoid receptor together with the negative correlation between hyperthermia and the number of glucocorticoid receptors in patients with sepsis or septic shock suggest that hypothalamic-pituitary-adrenal axis activation during critical illness is accompanied by peripheral adaptation in glucocorticoid receptor number and affinity." ], "offsets": [ [ 150, 2310 ] ] } ]

[ { "id": "1758", "type": "protein_family_or_group", "text": [ "glucocorticoid receptor" ], "offsets": [ [ 43, 66 ] ], "normalized": [] }, { "id": "1759", "type": "cell_type", "text": [ "peripheral blood mononuclear leucocyte" ], "offsets": [ [ 70, 108 ] ], "normalized": [] }, { "id": "1760", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 112, 120 ] ], "normalized": [] }, { "id": "1761", "type": "other_name", "text": [ "sepsis" ], "offsets": [ [ 126, 132 ] ], "normalized": [] }, { "id": "1762", "type": "other_name", "text": [ "septic shock" ], "offsets": [ [ 136, 148 ] ], "normalized": [] }, { "id": "1763", "type": "body_part", "text": [ "hypothalamic-pituitary-adrenal axis" ], "offsets": [ [ 179, 214 ] ], "normalized": [] }, { "id": "1764", "type": "protein_family_or_group", "text": [ "glucocorticoid receptor" ], "offsets": [ [ 335, 358 ] ], "normalized": [] }, { "id": "1765", "type": "tissue", "text": [ "glucocorticoid target tissues" ], "offsets": [ [ 362, 391 ] ], "normalized": [] }, { "id": "1766", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 395, 403 ] ], "normalized": [] }, { "id": "1767", "type": "other_name", "text": [ "sepsis" ], "offsets": [ [ 409, 415 ] ], "normalized": [] }, { "id": "1768", "type": "other_name", "text": [ "septic shock" ], "offsets": [ [ 419, 431 ] ], "normalized": [] }, { "id": "1769", "type": "other_name", "text": [ "hypercortisolaemia" ], "offsets": [ [ 456, 474 ] ], "normalized": [] }, { "id": "1770", "type": "other_name", "text": [ "hyperthermia" ], "offsets": [ [ 476, 488 ] ], "normalized": [] }, { "id": "1771", "type": "other_name", "text": [ "cellular composition" ], "offsets": [ [ 493, 513 ] ], "normalized": [] }, { "id": "1772", "type": "protein_family_or_group", "text": [ "glucocorticoid receptors" ], "offsets": [ [ 527, 551 ] ], "normalized": [] }, { "id": "1773", "type": "cell_type", "text": [ "peripheral blood mononuclear leucocytes" ], "offsets": [ [ 626, 665 ] ], "normalized": [] }, { "id": "1774", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 693, 701 ] ], "normalized": [] }, { "id": "1775", "type": "other_name", "text": [ "sepsis" ], "offsets": [ [ 707, 713 ] ], "normalized": [] }, { "id": "1776", "type": "other_name", "text": [ "septic shock" ], "offsets": [ [ 717, 729 ] ], "normalized": [] }, { "id": "1777", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 749, 757 ] ], "normalized": [] }, { "id": "1778", "type": "other_name", "text": [ "sepsis" ], "offsets": [ [ 775, 781 ] ], "normalized": [] }, { "id": "1779", "type": "other_name", "text": [ "septic shock" ], "offsets": [ [ 785, 797 ] ], "normalized": [] }, { "id": "1780", "type": "protein_family_or_group", "text": [ "glucocorticoid receptors" ], "offsets": [ [ 975, 999 ] ], "normalized": [] }, { "id": "1781", "type": "protein_family_or_group", "text": [ "glucocorticoid receptor" ], "offsets": [ [ 1196, 1219 ] ], "normalized": [] }, { "id": "1782", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 1409, 1417 ] ], "normalized": [] }, { "id": "1783", "type": "other_name", "text": [ "sepsis" ], "offsets": [ [ 1423, 1429 ] ], "normalized": [] }, { "id": "1784", "type": "other_name", "text": [ "septic shock" ], "offsets": [ [ 1433, 1445 ] ], "normalized": [] }, { "id": "1785", "type": "multi_cell", "text": [ "healthy controls" ], "offsets": [ [ 1461, 1477 ] ], "normalized": [] }, { "id": "1786", "type": "protein_family_or_group", "text": [ "glucocorticoid receptor" ], "offsets": [ [ 1516, 1539 ] ], "normalized": [] }, { "id": "1787", "type": "other_name", "text": [ "body temperature" ], "offsets": [ [ 1616, 1632 ] ], "normalized": [] }, { "id": "1788", "type": "protein_family_or_group", "text": [ "glucocorticoid receptors" ], "offsets": [ [ 1651, 1675 ] ], "normalized": [] }, { "id": "1789", "type": "other_name", "text": [ "circulating cortisol concentrations" ], "offsets": [ [ 1728, 1763 ] ], "normalized": [] }, { "id": "1790", "type": "lipid", "text": [ "cortisol" ], "offsets": [ [ 1740, 1748 ] ], "normalized": [] }, { "id": "1791", "type": "other_name", "text": [ "glucocorticoid receptor affinity" ], "offsets": [ [ 1768, 1800 ] ], "normalized": [] }, { "id": "1792", "type": "protein_family_or_group", "text": [ "glucocorticoid receptor" ], "offsets": [ [ 1768, 1791 ] ], "normalized": [] }, { "id": "1793", "type": "protein_family_or_group", "text": [ "glucocorticoid receptors" ], "offsets": [ [ 1874, 1898 ] ], "normalized": [] }, { "id": "1794", "type": "other_name", "text": [ "plasma cortisol concentrations" ], "offsets": [ [ 1902, 1932 ] ], "normalized": [] }, { "id": "1795", "type": "lipid", "text": [ "cortisol" ], "offsets": [ [ 1909, 1917 ] ], "normalized": [] }, { "id": "1796", "type": "protein_family_or_group", "text": [ "glucocorticoid receptor" ], "offsets": [ [ 1972, 1995 ] ], "normalized": [] }, { "id": "1797", "type": "other_name", "text": [ "hyperthermia" ], "offsets": [ [ 2043, 2055 ] ], "normalized": [] }, { "id": "1798", "type": "protein_family_or_group", "text": [ "glucocorticoid receptors" ], "offsets": [ [ 2074, 2098 ] ], "normalized": [] }, { "id": "1799", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 2102, 2110 ] ], "normalized": [] }, { "id": "1800", "type": "other_name", "text": [ "sepsis" ], "offsets": [ [ 2116, 2122 ] ], "normalized": [] }, { "id": "1801", "type": "other_name", "text": [ "septic shock" ], "offsets": [ [ 2126, 2138 ] ], "normalized": [] }, { "id": "1802", "type": "body_part", "text": [ "hypothalamic-pituitary-adrenal axis" ], "offsets": [ [ 2152, 2187 ] ], "normalized": [] }, { "id": "1803", "type": "other_name", "text": [ "peripheral adaptation" ], "offsets": [ [ 2241, 2262 ] ], "normalized": [] }, { "id": "1804", "type": "other_name", "text": [ "glucocorticoid receptor number" ], "offsets": [ [ 2266, 2296 ] ], "normalized": [] }, { "id": "1805", "type": "protein_family_or_group", "text": [ "glucocorticoid receptor" ], "offsets": [ [ 2074, 2097 ] ], "normalized": [] } ]

[]

[]

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[ { "id": "1807", "type": "title", "text": [ "Integrin-mediated tyrosine phosphorylation and cytokine message induction in monocytic cells. A possible signaling role for the Syk tyrosine kinase." ], "offsets": [ [ 0, 148 ] ] }, { "id": "1808", "type": "abstract", "text": [ "Activation of cytoplasmic tyrosine kinases is an important aspect of signal transduction mediated by integrins. In the human monocytic cell line THP-1, either integrin-dependent cell adhesion to fibronectin or ligation of beta 1 integrins with antibodies causes a rapid and intense tyrosine phosphorylation of two sets of proteins of about 65-75 and 120-125 kDa. In addition, integrin ligation leads to nuclear translocation of the p50 and p65 subunits of the NF-kappa B transcription factor, to activation of a reporter gene driven by a promoter containing NF-kappa B sites, and to increased levels of mRNAs for immediate-early genes, including the cytokine interleukin (IL)-1 beta. The tyrosine kinase inhibitors genistein and herbimycin A block both integrin-mediated tyrosine phosphorylation and increases in IL-1 beta message levels, indicating a causal relationship between the two events. The components tyrosine phosphorylated subsequent to cell adhesion include paxillin, pp125FAK, and the SH2 domain containing tyrosine kinase Syk. In contrast, integrin ligation with antibodies induces tyrosine phosphorylation of Syk but not of FAK or paxillin. In adhering cells, pre-treatment with cytochalasin D suppresses tyrosine phosphorylation of FAK and paxillin but not of Syk, while IL-1 beta message induction is unaffected. These observations indicate that the Syk tyrosine kinase may be an important component of an integrin signaling pathway in monocytic cells, leading to activation of NF-kappa B and to increased levels of cytokine messages." ], "offsets": [ [ 149, 1701 ] ] } ]

[ { "id": "1809", "type": "other_name", "text": [ "tyrosine phosphorylation" ], "offsets": [ [ 18, 42 ] ], "normalized": [] }, { "id": "1810", "type": "amino_acid_monomer", "text": [ "tyrosine" ], "offsets": [ [ 18, 26 ] ], "normalized": [] }, { "id": "1811", "type": "other_name", "text": [ "cytokine message induction" ], "offsets": [ [ 47, 73 ] ], "normalized": [] }, { "id": "1812", "type": "protein_family_or_group", "text": [ "cytokine" ], "offsets": [ [ 47, 55 ] ], "normalized": [] }, { "id": "1813", "type": "cell_type", "text": [ "monocytic cells" ], "offsets": [ [ 77, 92 ] ], "normalized": [] }, { "id": "1814", "type": "protein_family_or_group", "text": [ "Syk tyrosine kinase" ], "offsets": [ [ 128, 147 ] ], "normalized": [] }, { "id": "1815", "type": "amino_acid_monomer", "text": [ "tyrosine" ], "offsets": [ [ 132, 140 ] ], "normalized": [] }, { "id": "1816", "type": "protein_family_or_group", "text": [ "cytoplasmic tyrosine kinases" ], "offsets": [ [ 163, 191 ] ], "normalized": [] }, { "id": "1817", "type": "amino_acid_monomer", "text": [ "tyrosine" ], "offsets": [ [ 175, 183 ] ], "normalized": [] }, { "id": "1818", "type": "other_name", "text": [ "signal transduction" ], "offsets": [ [ 218, 237 ] ], "normalized": [] }, { "id": "1819", "type": "protein_family_or_group", "text": [ "integrins" ], "offsets": [ [ 250, 259 ] ], "normalized": [] }, { "id": "1820", "type": "cell_line", "text": [ "human monocytic cell line THP-1" ], "offsets": [ [ 268, 299 ] ], "normalized": [] }, { "id": "1821", "type": "other_name", "text": [ "integrin-dependent cell adhesion" ], "offsets": [ [ 308, 340 ] ], "normalized": [] }, { "id": "1822", "type": "protein_family_or_group", "text": [ "integrin" ], "offsets": [ [ 308, 316 ] ], "normalized": [] }, { "id": "1823", "type": "protein_family_or_group", "text": [ "fibronectin" ], "offsets": [ [ 344, 355 ] ], "normalized": [] }, { "id": "1824", "type": "protein_N/A", "text": [ "beta 1 integrins" ], "offsets": [ [ 371, 387 ] ], "normalized": [] }, { "id": "1825", "type": "protein_family_or_group", "text": [ "antibodies" ], "offsets": [ [ 393, 403 ] ], "normalized": [] }, { "id": "1826", "type": "other_name", "text": [ "tyrosine phosphorylation" ], "offsets": [ [ 431, 455 ] ], "normalized": [] }, { "id": "1827", "type": "amino_acid_monomer", "text": [ "tyrosine" ], "offsets": [ [ 431, 439 ] ], "normalized": [] }, { "id": "1828", "type": "protein_N/A", "text": [ "proteins" ], "offsets": [ [ 471, 479 ] ], "normalized": [] }, { "id": "1829", "type": "(AND protein_family_or_group protein_family_or_group)", "text": [ "65-75 and 120-125 kDa" ], "offsets": [ [ 489, 510 ] ], "normalized": [] }, { "id": "1830", "type": "", "text": [ "65-75" ], "offsets": [ [ 489, 494 ] ], "normalized": [] }, { "id": "1831", "type": "", "text": [ "120-125" ], "offsets": [ [ 499, 506 ] ], "normalized": [] }, { "id": "1832", "type": "", "text": [ "kDa" ], "offsets": [ [ 507, 510 ] ], "normalized": [] }, { "id": "1833", "type": "other_name", "text": [ "integrin ligation" ], "offsets": [ [ 525, 542 ] ], "normalized": [] }, { "id": "1834", "type": "protein_family_or_group", "text": [ "integrin" ], "offsets": [ [ 525, 533 ] ], "normalized": [] }, { "id": "1835", "type": "other_name", "text": [ "nuclear translocation" ], "offsets": [ [ 552, 573 ] ], "normalized": [] }, { "id": "1836", "type": "protein_subunit", "text": [ "p50" ], "offsets": [ [ 581, 584 ] ], "normalized": [] }, { "id": "1837", "type": "protein_subunit", "text": [ "p65 subunits" ], "offsets": [ [ 589, 601 ] ], "normalized": [] }, { "id": "1838", "type": "protein_complex", "text": [ "NF-kappa B transcription factor" ], "offsets": [ [ 609, 640 ] ], "normalized": [] }, { "id": "1839", "type": "DNA_family_or_group", "text": [ "reporter gene" ], "offsets": [ [ 661, 674 ] ], "normalized": [] }, { "id": "1840", "type": "DNA_domain_or_region", "text": [ "promoter" ], "offsets": [ [ 687, 695 ] ], "normalized": [] }, { "id": "1841", "type": "DNA_domain_or_region", "text": [ "NF-kappa B sites" ], "offsets": [ [ 707, 723 ] ], "normalized": [] }, { "id": "1842", "type": "RNA_family_or_group", "text": [ "mRNAs" ], "offsets": [ [ 752, 757 ] ], "normalized": [] }, { "id": "1843", "type": "DNA_family_or_group", "text": [ "immediate-early genes" ], "offsets": [ [ 762, 783 ] ], "normalized": [] }, { "id": "1844", "type": "protein_molecule", "text": [ "cytokine interleukin (IL)-1 beta" ], "offsets": [ [ 799, 831 ] ], "normalized": [] }, { "id": "1845", "type": "other_organic_compound", "text": [ "tyrosine kinase inhibitors" ], "offsets": [ [ 837, 863 ] ], "normalized": [] }, { "id": "1846", "type": "amino_acid_monomer", "text": [ "tyrosine" ], "offsets": [ [ 837, 845 ] ], "normalized": [] }, { "id": "1847", "type": "other_organic_compound", "text": [ "genistein" ], "offsets": [ [ 864, 873 ] ], "normalized": [] }, { "id": "1848", "type": "other_organic_compound", "text": [ "herbimycin A" ], "offsets": [ [ 878, 890 ] ], "normalized": [] }, { "id": "1849", "type": "other_name", "text": [ "integrin-mediated tyrosine phosphorylation" ], "offsets": [ [ 902, 944 ] ], "normalized": [] }, { "id": "1850", "type": "protein_family_or_group", "text": [ "integrin" ], "offsets": [ [ 902, 910 ] ], "normalized": [] }, { "id": "1851", "type": "other_name", "text": [ "tyrosine phosphorylation" ], "offsets": [ [ 920, 944 ] ], "normalized": [] }, { "id": "1852", "type": "amino_acid_monomer", "text": [ "tyrosine" ], "offsets": [ [ 920, 928 ] ], "normalized": [] }, { "id": "1853", "type": "other_name", "text": [ "IL-1 beta message levels" ], "offsets": [ [ 962, 986 ] ], "normalized": [] }, { "id": "1854", "type": "protein_molecule", "text": [ "IL-1 beta" ], "offsets": [ [ 962, 971 ] ], "normalized": [] }, { "id": "1855", "type": "amino_acid_monomer", "text": [ "tyrosine" ], "offsets": [ [ 1060, 1068 ] ], "normalized": [] }, { "id": "1856", "type": "other_name", "text": [ "cell adhesion" ], "offsets": [ [ 1098, 1111 ] ], "normalized": [] }, { "id": "1857", "type": "protein_molecule", "text": [ "paxillin" ], "offsets": [ [ 1120, 1128 ] ], "normalized": [] }, { "id": "1858", "type": "protein_molecule", "text": [ "pp125FAK" ], "offsets": [ [ 1130, 1138 ] ], "normalized": [] }, { "id": "1859", "type": "protein_molecule", "text": [ "SH2 domain containing tyrosine kinase Syk" ], "offsets": [ [ 1148, 1189 ] ], "normalized": [] }, { "id": "1860", "type": "protein_domain_or_region", "text": [ "SH2 domain" ], "offsets": [ [ 1148, 1158 ] ], "normalized": [] }, { "id": "1861", "type": "amino_acid_monomer", "text": [ "tyrosine" ], "offsets": [ [ 1170, 1178 ] ], "normalized": [] }, { "id": "1862", "type": "other_name", "text": [ "integrin ligation" ], "offsets": [ [ 1204, 1221 ] ], "normalized": [] }, { "id": "1863", "type": "protein_family_or_group", "text": [ "integrin" ], "offsets": [ [ 1204, 1212 ] ], "normalized": [] }, { "id": "1864", "type": "protein_family_or_group", "text": [ "antibodies" ], "offsets": [ [ 1227, 1237 ] ], "normalized": [] }, { "id": "1865", "type": "other_name", "text": [ "tyrosine phosphorylation" ], "offsets": [ [ 1246, 1270 ] ], "normalized": [] }, { "id": "1866", "type": "amino_acid_monomer", "text": [ "tyrosine" ], "offsets": [ [ 1246, 1254 ] ], "normalized": [] }, { "id": "1867", "type": "protein_molecule", "text": [ "Syk" ], "offsets": [ [ 1274, 1277 ] ], "normalized": [] }, { "id": "1868", "type": "protein_molecule", "text": [ "FAK" ], "offsets": [ [ 1289, 1292 ] ], "normalized": [] }, { "id": "1869", "type": "protein_molecule", "text": [ "paxillin" ], "offsets": [ [ 1296, 1304 ] ], "normalized": [] }, { "id": "1870", "type": "cell_type", "text": [ "adhering cells" ], "offsets": [ [ 1309, 1323 ] ], "normalized": [] }, { "id": "1871", "type": "other_organic_compound", "text": [ "cytochalasin D" ], "offsets": [ [ 1344, 1358 ] ], "normalized": [] }, { "id": "1872", "type": "other_name", "text": [ "tyrosine phosphorylation" ], "offsets": [ [ 1370, 1394 ] ], "normalized": [] }, { "id": "1873", "type": "amino_acid_monomer", "text": [ "tyrosine" ], "offsets": [ [ 1370, 1378 ] ], "normalized": [] }, { "id": "1874", "type": "protein_molecule", "text": [ "FAK" ], "offsets": [ [ 1398, 1401 ] ], "normalized": [] }, { "id": "1875", "type": "protein_molecule", "text": [ "paxillin" ], "offsets": [ [ 1406, 1414 ] ], "normalized": [] }, { "id": "1876", "type": "protein_molecule", "text": [ "Syk" ], "offsets": [ [ 1426, 1429 ] ], "normalized": [] }, { "id": "1877", "type": "protein_molecule", "text": [ "IL-1 beta" ], "offsets": [ [ 1437, 1446 ] ], "normalized": [] }, { "id": "1878", "type": "protein_molecule", "text": [ "Syk" ], "offsets": [ [ 1517, 1520 ] ], "normalized": [] }, { "id": "1879", "type": "amino_acid_monomer", "text": [ "tyrosine" ], "offsets": [ [ 1521, 1529 ] ], "normalized": [] }, { "id": "1880", "type": "other_name", "text": [ "integrin signaling pathway" ], "offsets": [ [ 1573, 1599 ] ], "normalized": [] }, { "id": "1881", "type": "protein_family_or_group", "text": [ "integrin" ], "offsets": [ [ 1573, 1581 ] ], "normalized": [] }, { "id": "1882", "type": "cell_type", "text": [ "monocytic cells" ], "offsets": [ [ 1603, 1618 ] ], "normalized": [] }, { "id": "1883", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 1645, 1655 ] ], "normalized": [] }, { "id": "1884", "type": "other_name", "text": [ "cytokine messages" ], "offsets": [ [ 1683, 1700 ] ], "normalized": [] }, { "id": "1885", "type": "protein_family_or_group", "text": [ "cytokine" ], "offsets": [ [ 1683, 1691 ] ], "normalized": [] } ]

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[ { "id": "1887", "type": "title", "text": [ "Inhibition of dexamethasone binding to human glucocorticoid receptor by New World primate cell extracts." ], "offsets": [ [ 0, 104 ] ] }, { "id": "1888", "type": "abstract", "text": [ "To determine if New World primates express an inhibitor that influences glucocorticoid receptor (GR) binding characteristics, we examined [3H]dexamethasone binding in cytosol prepared from B95-8 lymphoid cells, derived from the cotton top tamarin (Saguinus oedipus), in combination with cytosol prepared from human or rat tissues. B95-8 cytosol inhibited specific binding of [3H]dexamethasone (P < 0.01) when mixed with cytosol prepared from either a human lymphoid cell line (HL) or rat thymus. The inhibitory activity was heat labile and trypsin sensitive. Peak inhibitory activity was found in the 150-200 kd fractions after Sephacryl G-200 ultrafiltration. Scatchard analysis of [3H]dexamethasone binding using mixed cytosol showed a diminished GR apparent binding affinity when compared to HL cytosol. Kinetic studies using mixed cytosol indicated that B95-8 cytosol did not affect the apparent dissociation rate of [3H]dexamethasone. These data demonstrate that B95-8 cells contain a competitive inhibitor that prevents binding of dexamethasone to its cognate receptor." ], "offsets": [ [ 105, 1180 ] ] } ]

[ { "id": "1889", "type": "lipid", "text": [ "dexamethasone" ], "offsets": [ [ 14, 27 ] ], "normalized": [] }, { "id": "1890", "type": "protein_family_or_group", "text": [ "human glucocorticoid receptor" ], "offsets": [ [ 39, 68 ] ], "normalized": [] }, { "id": "1891", "type": "cell_component", "text": [ "New World primate cell extracts" ], "offsets": [ [ 72, 103 ] ], "normalized": [] }, { "id": "1892", "type": "multi_cell", "text": [ "New World primate" ], "offsets": [ [ 72, 89 ] ], "normalized": [] }, { "id": "1893", "type": "multi_cell", "text": [ "New World primates" ], "offsets": [ [ 121, 139 ] ], "normalized": [] }, { "id": "1894", "type": "other_name", "text": [ "glucocorticoid receptor (GR) binding characteristics" ], "offsets": [ [ 177, 229 ] ], "normalized": [] }, { "id": "1895", "type": "protein_family_or_group", "text": [ "glucocorticoid receptor" ], "offsets": [ [ 177, 200 ] ], "normalized": [] }, { "id": "1896", "type": "protein_domain_or_region", "text": [ "GR" ], "offsets": [ [ 202, 204 ] ], "normalized": [] }, { "id": "1897", "type": "lipid", "text": [ "[3H]dexamethasone" ], "offsets": [ [ 243, 260 ] ], "normalized": [] }, { "id": "1898", "type": "cell_component", "text": [ "cytosol" ], "offsets": [ [ 272, 279 ] ], "normalized": [] }, { "id": "1899", "type": "cell_line", "text": [ "B95-8 lymphoid cells" ], "offsets": [ [ 294, 314 ] ], "normalized": [] }, { "id": "1900", "type": "multi_cell", "text": [ "cotton top tamarin" ], "offsets": [ [ 333, 351 ] ], "normalized": [] }, { "id": "1901", "type": "multi_cell", "text": [ "Saguinus oedipus" ], "offsets": [ [ 353, 369 ] ], "normalized": [] }, { "id": "1902", "type": "cell_component", "text": [ "cytosol" ], "offsets": [ [ 392, 399 ] ], "normalized": [] }, { "id": "1903", "type": "tissue", "text": [ "human or rat tissues" ], "offsets": [ [ 414, 434 ] ], "normalized": [] }, { "id": "1904", "type": "tissue", "text": [ "human" ], "offsets": [ [ 414, 419 ] ], "normalized": [] }, { "id": "1905", "type": "multi_cell", "text": [ "human" ], "offsets": [ [ 414, 419 ] ], "normalized": [] }, { "id": "1906", "type": "tissue", "text": [ "rat tissues" ], "offsets": [ [ 423, 434 ] ], "normalized": [] }, { "id": "1907", "type": "multi_cell", "text": [ "rat" ], "offsets": [ [ 423, 426 ] ], "normalized": [] }, { "id": "1908", "type": "cell_component", "text": [ "B95-8 cytosol" ], "offsets": [ [ 436, 449 ] ], "normalized": [] }, { "id": "1909", "type": "cell_component", "text": [ "cytosol" ], "offsets": [ [ 442, 449 ] ], "normalized": [] }, { "id": "1910", "type": "lipid", "text": [ "[3H]dexamethasone" ], "offsets": [ [ 480, 497 ] ], "normalized": [] }, { "id": "1911", "type": "cell_component", "text": [ "cytosol" ], "offsets": [ [ 525, 532 ] ], "normalized": [] }, { "id": "1912", "type": "cell_line", "text": [ "human lymphoid cell line" ], "offsets": [ [ 556, 580 ] ], "normalized": [] }, { "id": "1913", "type": "cell_line", "text": [ "HL" ], "offsets": [ [ 582, 584 ] ], "normalized": [] }, { "id": "1914", "type": "body_part", "text": [ "rat thymus" ], "offsets": [ [ 589, 599 ] ], "normalized": [] }, { "id": "1915", "type": "multi_cell", "text": [ "rat" ], "offsets": [ [ 589, 592 ] ], "normalized": [] }, { "id": "1916", "type": "other_name", "text": [ "inhibitory activity" ], "offsets": [ [ 605, 624 ] ], "normalized": [] }, { "id": "1917", "type": "other_name", "text": [ "heat labile" ], "offsets": [ [ 629, 640 ] ], "normalized": [] }, { "id": "1918", "type": "other_name", "text": [ "trypsin sensitive" ], "offsets": [ [ 645, 662 ] ], "normalized": [] }, { "id": "1919", "type": "protein_molecule", "text": [ "trypsin" ], "offsets": [ [ 645, 652 ] ], "normalized": [] }, { "id": "1920", "type": "other_name", "text": [ "inhibitory activity" ], "offsets": [ [ 669, 688 ] ], "normalized": [] }, { "id": "1921", "type": "other_name", "text": [ "Sephacryl G-200 ultrafiltration" ], "offsets": [ [ 733, 764 ] ], "normalized": [] }, { "id": "1922", "type": "other_name", "text": [ "Scatchard analysis" ], "offsets": [ [ 766, 784 ] ], "normalized": [] }, { "id": "1923", "type": "lipid", "text": [ "[3H]dexamethasone" ], "offsets": [ [ 788, 805 ] ], "normalized": [] }, { "id": "1924", "type": "cell_component", "text": [ "cytosol" ], "offsets": [ [ 826, 833 ] ], "normalized": [] }, { "id": "1925", "type": "protein_domain_or_region", "text": [ "GR" ], "offsets": [ [ 854, 856 ] ], "normalized": [] }, { "id": "1926", "type": "other_name", "text": [ "binding affinity" ], "offsets": [ [ 866, 882 ] ], "normalized": [] }, { "id": "1927", "type": "cell_component", "text": [ "HL cytosol" ], "offsets": [ [ 900, 910 ] ], "normalized": [] }, { "id": "1928", "type": "cell_component", "text": [ "cytosol" ], "offsets": [ [ 903, 910 ] ], "normalized": [] }, { "id": "1929", "type": "other_name", "text": [ "Kinetic studies" ], "offsets": [ [ 912, 927 ] ], "normalized": [] }, { "id": "1930", "type": "cell_component", "text": [ "cytosol" ], "offsets": [ [ 940, 947 ] ], "normalized": [] }, { "id": "1931", "type": "cell_component", "text": [ "B95-8 cytosol" ], "offsets": [ [ 963, 976 ] ], "normalized": [] }, { "id": "1932", "type": "cell_component", "text": [ "cytosol" ], "offsets": [ [ 969, 976 ] ], "normalized": [] }, { "id": "1933", "type": "lipid", "text": [ "[3H]dexamethasone" ], "offsets": [ [ 1026, 1043 ] ], "normalized": [] }, { "id": "1934", "type": "cell_type", "text": [ "B95-8 cells" ], "offsets": [ [ 1073, 1084 ] ], "normalized": [] }, { "id": "1935", "type": "lipid", "text": [ "dexamethasone" ], "offsets": [ [ 1142, 1155 ] ], "normalized": [] }, { "id": "1936", "type": "protein_family_or_group", "text": [ "cognate receptor" ], "offsets": [ [ 1163, 1179 ] ], "normalized": [] } ]

[]

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[ { "id": "1938", "type": "title", "text": [ "Disruption of a GATA motif in the Duffy gene promoter abolishes erythroid gene expression in Duffy-negative individuals." ], "offsets": [ [ 0, 120 ] ] }, { "id": "1939", "type": "abstract", "text": [ "The mRNA for the Duffy blood group antigen, the erythrocyte receptor for the Plasmodium vivax malaria parasite, has recently been cloned and shown to encode a widely expressed chemokine receptor. Here, we show that the Duffy antigen/chemokine receptor gene (DARC) is composed of a single exon and that most Duffy-negative blacks carry a silent FY*B allele with a single T to C substitution at nucleotide -46. This mutation impairs the promoter activity in erythroid cells by disrupting a binding site for the GATA1 erythroid transcription factor. With the recent characterization of the FY*A and FY*B alleles, these findings provide the molecular basis of the Duffy blood group system and an explanation for the erythroid-specific repression of the DARC gene in Duffy-negative individuals." ], "offsets": [ [ 121, 910 ] ] } ]

[ { "id": "1940", "type": "DNA_domain_or_region", "text": [ "GATA motif" ], "offsets": [ [ 16, 26 ] ], "normalized": [] }, { "id": "1941", "type": "DNA_domain_or_region", "text": [ "Duffy gene promoter" ], "offsets": [ [ 34, 53 ] ], "normalized": [] }, { "id": "1942", "type": "other_name", "text": [ "erythroid gene expression" ], "offsets": [ [ 64, 89 ] ], "normalized": [] }, { "id": "1943", "type": "DNA_domain_or_region", "text": [ "erythroid gene" ], "offsets": [ [ 64, 78 ] ], "normalized": [] }, { "id": "1944", "type": "multi_cell", "text": [ "Duffy-negative individuals" ], "offsets": [ [ 93, 119 ] ], "normalized": [] }, { "id": "1945", "type": "RNA_family_or_group", "text": [ "mRNA" ], "offsets": [ [ 125, 129 ] ], "normalized": [] }, { "id": "1946", "type": "protein_molecule", "text": [ "Duffy blood group antigen" ], "offsets": [ [ 138, 163 ] ], "normalized": [] }, { "id": "1947", "type": "protein_family_or_group", "text": [ "erythrocyte receptor" ], "offsets": [ [ 169, 189 ] ], "normalized": [] }, { "id": "1948", "type": "multi_cell", "text": [ "Plasmodium vivax malaria parasite" ], "offsets": [ [ 198, 231 ] ], "normalized": [] }, { "id": "1949", "type": "multi_cell", "text": [ "Plasmodium vivax malaria" ], "offsets": [ [ 198, 222 ] ], "normalized": [] }, { "id": "1950", "type": "protein_family_or_group", "text": [ "chemokine receptor" ], "offsets": [ [ 297, 315 ] ], "normalized": [] }, { "id": "1951", "type": "DNA_domain_or_region", "text": [ "Duffy antigen/chemokine receptor gene" ], "offsets": [ [ 340, 377 ] ], "normalized": [] }, { "id": "1952", "type": "protein_molecule", "text": [ "Duffy antigen/chemokine receptor" ], "offsets": [ [ 340, 372 ] ], "normalized": [] }, { "id": "1953", "type": "DNA_domain_or_region", "text": [ "DARC" ], "offsets": [ [ 379, 383 ] ], "normalized": [] }, { "id": "1954", "type": "DNA_family_or_group", "text": [ "exon" ], "offsets": [ [ 409, 413 ] ], "normalized": [] }, { "id": "1955", "type": "multi_cell", "text": [ "Duffy-negative blacks" ], "offsets": [ [ 428, 449 ] ], "normalized": [] }, { "id": "1956", "type": "DNA_domain_or_region", "text": [ "silent FY*B allele" ], "offsets": [ [ 458, 476 ] ], "normalized": [] }, { "id": "1957", "type": "other_name", "text": [ "T to C substitution" ], "offsets": [ [ 491, 510 ] ], "normalized": [] }, { "id": "1958", "type": "nucleotide", "text": [ "nucleotide -46" ], "offsets": [ [ 514, 528 ] ], "normalized": [] }, { "id": "1959", "type": "other_name", "text": [ "promoter activity" ], "offsets": [ [ 556, 573 ] ], "normalized": [] }, { "id": "1960", "type": "cell_type", "text": [ "erythroid cells" ], "offsets": [ [ 577, 592 ] ], "normalized": [] }, { "id": "1961", "type": "DNA_domain_or_region", "text": [ "binding site" ], "offsets": [ [ 609, 621 ] ], "normalized": [] }, { "id": "1962", "type": "protein_domain_or_region", "text": [ "GATA1 erythroid transcription factor" ], "offsets": [ [ 630, 666 ] ], "normalized": [] }, { "id": "1963", "type": "(AND DNA_domain_or_region DNA_domain_or_region)", "text": [ "FY*A and FY*B alleles" ], "offsets": [ [ 708, 729 ] ], "normalized": [] }, { "id": "1964", "type": "", "text": [ "FY*A" ], "offsets": [ [ 708, 712 ] ], "normalized": [] }, { "id": "1965", "type": "", "text": [ "FY*B" ], "offsets": [ [ 717, 721 ] ], "normalized": [] }, { "id": "1966", "type": "", "text": [ "alleles" ], "offsets": [ [ 722, 729 ] ], "normalized": [] }, { "id": "1967", "type": "other_name", "text": [ "Duffy blood group system" ], "offsets": [ [ 781, 805 ] ], "normalized": [] }, { "id": "1968", "type": "other_name", "text": [ "erythroid-specific repression" ], "offsets": [ [ 833, 862 ] ], "normalized": [] }, { "id": "1969", "type": "DNA_domain_or_region", "text": [ "DARC gene" ], "offsets": [ [ 870, 879 ] ], "normalized": [] }, { "id": "1970", "type": "multi_cell", "text": [ "Duffy-negative individuals" ], "offsets": [ [ 883, 909 ] ], "normalized": [] } ]

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[ { "id": "1972", "type": "title", "text": [ "Activation of pp90rsk and early growth response-1 gene expression by pokeweed mitogen in human B cells." ], "offsets": [ [ 0, 103 ] ] }, { "id": "1973", "type": "abstract", "text": [ "The present studies have examined the effects of pokeweed mitogen (PWM) on the induction of early growth response-1 gene (EGR-1) in normal human B cells. PWM regulates EGR-1 gene expression by both transcriptional and post-transcriptional mechanisms. Transient transfection assays with EGR-1 promoter fragments linked to the chloramphenicol acetyltransferase (CAT) gene demonstrated that PWM induced EGR-1 transcription is conferred by the CArG motif (C C[AT]6GG) in the EGR-1 promoter. The results further demonstrated the activation of S6 kinase (pp90rsk), evidenced by phosphorylation of S6 and serum response factor (SRF) peptides, in PWM treated B cells. Taken together, these findings suggest that PWM is able to initiate an intracytoplasmic signalling cascade and EGR-1 induction in normal human B cells." ], "offsets": [ [ 104, 915 ] ] } ]

[ { "id": "1974", "type": "protein_molecule", "text": [ "pp90rsk" ], "offsets": [ [ 14, 21 ] ], "normalized": [] }, { "id": "1975", "type": "other_name", "text": [ "early growth response-1 gene expression" ], "offsets": [ [ 26, 65 ] ], "normalized": [] }, { "id": "1976", "type": "DNA_domain_or_region", "text": [ "early growth response-1 gene" ], "offsets": [ [ 26, 54 ] ], "normalized": [] }, { "id": "1977", "type": "protein_molecule", "text": [ "pokeweed mitogen" ], "offsets": [ [ 69, 85 ] ], "normalized": [] }, { "id": "1978", "type": "cell_type", "text": [ "human B cells" ], "offsets": [ [ 89, 102 ] ], "normalized": [] }, { "id": "1979", "type": "protein_molecule", "text": [ "pokeweed mitogen" ], "offsets": [ [ 153, 169 ] ], "normalized": [] }, { "id": "1980", "type": "protein_molecule", "text": [ "PWM" ], "offsets": [ [ 171, 174 ] ], "normalized": [] }, { "id": "1981", "type": "DNA_domain_or_region", "text": [ "early growth response-1 gene" ], "offsets": [ [ 196, 224 ] ], "normalized": [] }, { "id": "1982", "type": "DNA_domain_or_region", "text": [ "EGR-1" ], "offsets": [ [ 226, 231 ] ], "normalized": [] }, { "id": "1983", "type": "cell_type", "text": [ "normal human B cells" ], "offsets": [ [ 236, 256 ] ], "normalized": [] }, { "id": "1984", "type": "cell_type", "text": [ "human B cells" ], "offsets": [ [ 243, 256 ] ], "normalized": [] }, { "id": "1985", "type": "protein_molecule", "text": [ "PWM" ], "offsets": [ [ 258, 261 ] ], "normalized": [] }, { "id": "1986", "type": "other_name", "text": [ "EGR-1 gene expression" ], "offsets": [ [ 272, 293 ] ], "normalized": [] }, { "id": "1987", "type": "DNA_domain_or_region", "text": [ "EGR-1" ], "offsets": [ [ 272, 277 ] ], "normalized": [] }, { "id": "1988", "type": "(AND other_name other_name)", "text": [ "transcriptional and post-transcriptional mechanisms" ], "offsets": [ [ 302, 353 ] ], "normalized": [] }, { "id": "1989", "type": "", "text": [ "transcriptional" ], "offsets": [ [ 302, 317 ] ], "normalized": [] }, { "id": "1990", "type": "", "text": [ "post-transcriptional" ], "offsets": [ [ 322, 342 ] ], "normalized": [] }, { "id": "1991", "type": "", "text": [ "mechanisms" ], "offsets": [ [ 343, 353 ] ], "normalized": [] }, { "id": "1992", "type": "other_name", "text": [ "Transient transfection assays" ], "offsets": [ [ 355, 384 ] ], "normalized": [] }, { "id": "1993", "type": "DNA_molecule", "text": [ "EGR-1 promoter fragments" ], "offsets": [ [ 390, 414 ] ], "normalized": [] }, { "id": "1994", "type": "DNA_domain_or_region", "text": [ "EGR-1" ], "offsets": [ [ 390, 395 ] ], "normalized": [] }, { "id": "1995", "type": "DNA_domain_or_region", "text": [ "chloramphenicol acetyltransferase (CAT) gene" ], "offsets": [ [ 429, 473 ] ], "normalized": [] }, { "id": "1996", "type": "protein_molecule", "text": [ "chloramphenicol acetyltransferase" ], "offsets": [ [ 429, 462 ] ], "normalized": [] }, { "id": "1997", "type": "protein_molecule", "text": [ "CAT" ], "offsets": [ [ 464, 467 ] ], "normalized": [] }, { "id": "1998", "type": "protein_molecule", "text": [ "PWM" ], "offsets": [ [ 492, 495 ] ], "normalized": [] }, { "id": "1999", "type": "other_name", "text": [ "EGR-1 transcription" ], "offsets": [ [ 504, 523 ] ], "normalized": [] }, { "id": "2000", "type": "DNA_domain_or_region", "text": [ "EGR-1" ], "offsets": [ [ 504, 509 ] ], "normalized": [] }, { "id": "2001", "type": "DNA_domain_or_region", "text": [ "CArG motif" ], "offsets": [ [ 544, 554 ] ], "normalized": [] }, { "id": "2002", "type": "DNA_domain_or_region", "text": [ "C C[AT]6GG" ], "offsets": [ [ 556, 566 ] ], "normalized": [] }, { "id": "2003", "type": "DNA_domain_or_region", "text": [ "EGR-1 promoter" ], "offsets": [ [ 390, 404 ] ], "normalized": [] }, { "id": "2004", "type": "DNA_domain_or_region", "text": [ "EGR-1" ], "offsets": [ [ 575, 580 ] ], "normalized": [] }, { "id": "2005", "type": "protein_molecule", "text": [ "S6 kinase" ], "offsets": [ [ 642, 651 ] ], "normalized": [] }, { "id": "2006", "type": "protein_molecule", "text": [ "pp90rsk" ], "offsets": [ [ 653, 660 ] ], "normalized": [] }, { "id": "2007", "type": "other_name", "text": [ "phosphorylation" ], "offsets": [ [ 676, 691 ] ], "normalized": [] }, { "id": "2008", "type": "protein_molecule", "text": [ "S6" ], "offsets": [ [ 642, 644 ] ], "normalized": [] }, { "id": "2009", "type": "peptide", "text": [ "serum response factor (SRF) peptides" ], "offsets": [ [ 702, 738 ] ], "normalized": [] }, { "id": "2010", "type": "cell_line", "text": [ "PWM treated B cells" ], "offsets": [ [ 743, 762 ] ], "normalized": [] }, { "id": "2011", "type": "protein_molecule", "text": [ "PWM" ], "offsets": [ [ 743, 746 ] ], "normalized": [] }, { "id": "2012", "type": "protein_molecule", "text": [ "PWM" ], "offsets": [ [ 808, 811 ] ], "normalized": [] }, { "id": "2013", "type": "other_name", "text": [ "intracytoplasmic signalling cascade" ], "offsets": [ [ 835, 870 ] ], "normalized": [] }, { "id": "2014", "type": "other_name", "text": [ "EGR-1 induction" ], "offsets": [ [ 875, 890 ] ], "normalized": [] }, { "id": "2015", "type": "DNA_domain_or_region", "text": [ "EGR-1" ], "offsets": [ [ 875, 880 ] ], "normalized": [] }, { "id": "2016", "type": "cell_type", "text": [ "normal human B cells" ], "offsets": [ [ 894, 914 ] ], "normalized": [] }, { "id": "2017", "type": "cell_type", "text": [ "human B cells" ], "offsets": [ [ 901, 914 ] ], "normalized": [] } ]

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[ { "id": "2019", "type": "title", "text": [ "A conserved motif in the promoters of several cytokines expressed by human Th2-type lymphocytes." ], "offsets": [ [ 0, 96 ] ] }, { "id": "2020", "type": "abstract", "text": [ "We have recently found a novel conserved motif in the promoters of several T-cell-expressed cytokines [human interleukin-2, -4, -5 and -13 and human and mouse granulocyte/macrophage-colony stimulating factor (GM-CSF)]. It contains a core sequence CTTGG ... CCAAG which is present as part of larger palindromic sequences in each gene. This suggest that they may interact with a new family of trans-acting factors. In transfection assays, the human GM-CSF element has a strong positive effect on the expression of a reporter gene by the human T cell line Jurkat J6 upon stimulation. In DNA mobility shift assays, this sequence can give either six different specific bands which are competed out by different parts of the sequence or one specific band which is competed out by each of the inverted repeats, depending on the reconstitution conditions. In different genes, the core sequences are separated by integer numbers of helical turns. Considering the strong positive regulatory effect of this element and its presence in several T-cell-expressed cytokine genes, it may be crucial to the coordinated expression of these cytokines in T helper cells." ], "offsets": [ [ 97, 1247 ] ] } ]

[ { "id": "2021", "type": "DNA_domain_or_region", "text": [ "conserved motif" ], "offsets": [ [ 2, 17 ] ], "normalized": [] }, { "id": "2022", "type": "DNA_family_or_group", "text": [ "promoters" ], "offsets": [ [ 25, 34 ] ], "normalized": [] }, { "id": "2023", "type": "protein_family_or_group", "text": [ "cytokines" ], "offsets": [ [ 46, 55 ] ], "normalized": [] }, { "id": "2024", "type": "cell_line", "text": [ "human Th2-type lymphocytes" ], "offsets": [ [ 69, 95 ] ], "normalized": [] }, { "id": "2025", "type": "DNA_domain_or_region", "text": [ "conserved motif" ], "offsets": [ [ 128, 143 ] ], "normalized": [] }, { "id": "2026", "type": "DNA_domain_or_region", "text": [ "promoters" ], "offsets": [ [ 151, 160 ] ], "normalized": [] }, { "id": "2027", "type": "protein_family_or_group", "text": [ "T-cell-expressed cytokines" ], "offsets": [ [ 172, 198 ] ], "normalized": [] }, { "id": "2028", "type": "protein_family_or_group", "text": [ "cytokines" ], "offsets": [ [ 189, 198 ] ], "normalized": [] }, { "id": "2029", "type": "(AND protein_molecule protein_molecule protein_molecule protein_molecule)", "text": [ "human interleukin-2, -4, -5 and -13" ], "offsets": [ [ 200, 235 ] ], "normalized": [] }, { "id": "2030", "type": "", "text": [ "human interleukin" ], "offsets": [ [ 200, 217 ] ], "normalized": [] }, { "id": "2031", "type": "", "text": [ "-2" ], "offsets": [ [ 217, 219 ] ], "normalized": [] }, { "id": "2032", "type": "", "text": [ "-4" ], "offsets": [ [ 221, 223 ] ], "normalized": [] }, { "id": "2033", "type": "", "text": [ "-5" ], "offsets": [ [ 225, 227 ] ], "normalized": [] }, { "id": "2034", "type": "", "text": [ "-13" ], "offsets": [ [ 232, 235 ] ], "normalized": [] }, { "id": "2035", "type": "(AND protein_molecule protein_molecule)", "text": [ "human and mouse granulocyte/macrophage-colony stimulating factor" ], "offsets": [ [ 240, 304 ] ], "normalized": [] }, { "id": "2036", "type": "", "text": [ "human" ], "offsets": [ [ 200, 205 ] ], "normalized": [] }, { "id": "2037", "type": "", "text": [ "mouse" ], "offsets": [ [ 250, 255 ] ], "normalized": [] }, { "id": "2038", "type": "", "text": [ "granulocyte/macrophage-colony stimulating factor" ], "offsets": [ [ 256, 304 ] ], "normalized": [] }, { "id": "2039", "type": "protein_molecule", "text": [ "GM-CSF" ], "offsets": [ [ 306, 312 ] ], "normalized": [] }, { "id": "2040", "type": "DNA_domain_or_region", "text": [ "core sequence" ], "offsets": [ [ 330, 343 ] ], "normalized": [] }, { "id": "2041", "type": "polynucleotide", "text": [ "CTTGG ... CCAAG" ], "offsets": [ [ 344, 359 ] ], "normalized": [] }, { "id": "2042", "type": "DNA_family_or_group", "text": [ "palindromic sequences" ], "offsets": [ [ 395, 416 ] ], "normalized": [] }, { "id": "2043", "type": "protein_family_or_group", "text": [ "trans-acting factors" ], "offsets": [ [ 488, 508 ] ], "normalized": [] }, { "id": "2044", "type": "other_name", "text": [ "transfection assays" ], "offsets": [ [ 513, 532 ] ], "normalized": [] }, { "id": "2045", "type": "DNA_domain_or_region", "text": [ "human GM-CSF element" ], "offsets": [ [ 538, 558 ] ], "normalized": [] }, { "id": "2046", "type": "protein_molecule", "text": [ "GM-CSF" ], "offsets": [ [ 544, 550 ] ], "normalized": [] }, { "id": "2047", "type": "DNA_family_or_group", "text": [ "reporter gene" ], "offsets": [ [ 611, 624 ] ], "normalized": [] }, { "id": "2048", "type": "cell_line", "text": [ "human T cell line" ], "offsets": [ [ 632, 649 ] ], "normalized": [] }, { "id": "2049", "type": "cell_line", "text": [ "Jurkat J6" ], "offsets": [ [ 650, 659 ] ], "normalized": [] }, { "id": "2050", "type": "other_name", "text": [ "stimulation" ], "offsets": [ [ 665, 676 ] ], "normalized": [] }, { "id": "2051", "type": "other_name", "text": [ "DNA mobility shift assays" ], "offsets": [ [ 681, 706 ] ], "normalized": [] }, { "id": "2052", "type": "other_name", "text": [ "specific bands" ], "offsets": [ [ 752, 766 ] ], "normalized": [] }, { "id": "2053", "type": "other_name", "text": [ "specific band" ], "offsets": [ [ 752, 765 ] ], "normalized": [] }, { "id": "2054", "type": "other_name", "text": [ "reconstitution conditions" ], "offsets": [ [ 918, 943 ] ], "normalized": [] }, { "id": "2055", "type": "DNA_family_or_group", "text": [ "genes" ], "offsets": [ [ 958, 963 ] ], "normalized": [] }, { "id": "2056", "type": "DNA_domain_or_region", "text": [ "core sequences" ], "offsets": [ [ 969, 983 ] ], "normalized": [] }, { "id": "2057", "type": "DNA_substructure", "text": [ "helical turns" ], "offsets": [ [ 1020, 1033 ] ], "normalized": [] }, { "id": "2058", "type": "other_name", "text": [ "strong positive regulatory effect" ], "offsets": [ [ 1051, 1084 ] ], "normalized": [] }, { "id": "2059", "type": "DNA_family_or_group", "text": [ "element" ], "offsets": [ [ 1093, 1100 ] ], "normalized": [] }, { "id": "2060", "type": "DNA_family_or_group", "text": [ "T-cell-expressed cytokine genes" ], "offsets": [ [ 1129, 1160 ] ], "normalized": [] }, { "id": "2061", "type": "protein_family_or_group", "text": [ "cytokines" ], "offsets": [ [ 1219, 1228 ] ], "normalized": [] }, { "id": "2062", "type": "cell_type", "text": [ "T helper cells" ], "offsets": [ [ 1232, 1246 ] ], "normalized": [] } ]

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[]

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[ { "id": "2064", "type": "title", "text": [ "cDNA cloning of a NGFI-B/nur77-related transcription factor from an apoptotic human T cell line." ], "offsets": [ [ 0, 96 ] ] }, { "id": "2065", "type": "abstract", "text": [ "A human T lymphoid cell line, PEER, dies by apoptosis in the presence of PMA and calcium ionophore. A new gene, TINUR, was cloned from apoptotic PEER cells. The expression of the TINUR gene is induced within 1 h after the cross-linking of the T cell Ag receptor complex. TINUR belongs to the NGFI-B/nur77 family of the steroid receptor superfamily and is an orphan receptor. TINUR binds to the same DNA sequence as NGFI-B/nur77. We also propose that the NGFI-B/nur77 family can be classified into two subtypes." ], "offsets": [ [ 97, 607 ] ] } ]

[ { "id": "2066", "type": "other_name", "text": [ "cDNA cloning" ], "offsets": [ [ 0, 12 ] ], "normalized": [] }, { "id": "2067", "type": "DNA_family_or_group", "text": [ "cDNA" ], "offsets": [ [ 0, 4 ] ], "normalized": [] }, { "id": "2068", "type": "protein_family_or_group", "text": [ "NGFI-B/nur77-related transcription factor" ], "offsets": [ [ 18, 59 ] ], "normalized": [] }, { "id": "2069", "type": "cell_line", "text": [ "apoptotic human T cell line" ], "offsets": [ [ 68, 95 ] ], "normalized": [] }, { "id": "2070", "type": "cell_line", "text": [ "human T lymphoid cell line" ], "offsets": [ [ 99, 125 ] ], "normalized": [] }, { "id": "2071", "type": "cell_line", "text": [ "PEER" ], "offsets": [ [ 127, 131 ] ], "normalized": [] }, { "id": "2072", "type": "other_name", "text": [ "apoptosis" ], "offsets": [ [ 141, 150 ] ], "normalized": [] }, { "id": "2073", "type": "other_organic_compound", "text": [ "PMA" ], "offsets": [ [ 170, 173 ] ], "normalized": [] }, { "id": "2074", "type": "other_organic_compound", "text": [ "calcium ionophore" ], "offsets": [ [ 178, 195 ] ], "normalized": [] }, { "id": "2075", "type": "DNA_domain_or_region", "text": [ "gene" ], "offsets": [ [ 203, 207 ] ], "normalized": [] }, { "id": "2076", "type": "DNA_domain_or_region", "text": [ "TINUR" ], "offsets": [ [ 209, 214 ] ], "normalized": [] }, { "id": "2077", "type": "cell_line", "text": [ "apoptotic PEER cells" ], "offsets": [ [ 232, 252 ] ], "normalized": [] }, { "id": "2078", "type": "DNA_domain_or_region", "text": [ "TINUR gene" ], "offsets": [ [ 276, 286 ] ], "normalized": [] }, { "id": "2079", "type": "protein_subunit", "text": [ "T cell Ag receptor complex" ], "offsets": [ [ 340, 366 ] ], "normalized": [] }, { "id": "2080", "type": "DNA_domain_or_region", "text": [ "TINUR" ], "offsets": [ [ 368, 373 ] ], "normalized": [] }, { "id": "2081", "type": "protein_family_or_group", "text": [ "NGFI-B/nur77 family" ], "offsets": [ [ 389, 408 ] ], "normalized": [] }, { "id": "2082", "type": "protein_family_or_group", "text": [ "steroid receptor superfamily" ], "offsets": [ [ 416, 444 ] ], "normalized": [] }, { "id": "2083", "type": "protein_family_or_group", "text": [ "orphan receptor" ], "offsets": [ [ 455, 470 ] ], "normalized": [] }, { "id": "2084", "type": "DNA_domain_or_region", "text": [ "TINUR" ], "offsets": [ [ 472, 477 ] ], "normalized": [] }, { "id": "2085", "type": "DNA_domain_or_region", "text": [ "DNA sequence" ], "offsets": [ [ 496, 508 ] ], "normalized": [] }, { "id": "2086", "type": "protein_molecule", "text": [ "NGFI-B/nur77" ], "offsets": [ [ 512, 524 ] ], "normalized": [] }, { "id": "2087", "type": "protein_family_or_group", "text": [ "NGFI-B/nur77 family" ], "offsets": [ [ 551, 570 ] ], "normalized": [] } ]

[]

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[ { "id": "2089", "type": "title", "text": [ "Aspirin inhibits nuclear factor-kappa B mobilization and monocyte adhesion in stimulated human endothelial cells." ], "offsets": [ [ 0, 113 ] ] }, { "id": "2090", "type": "abstract", "text": [ "BACKGROUND: The induction of vascular cell adhesion molecule-1 (VCAM-1) and E-selectin by tumor necrosis factor-alpha (TNF) is mediated by mobilization of the transcription factor nuclear factor-kappa B (NF-kappa B). Since salicylates have been reported to inhibit NF-kappa B activation by preventing the degradation of its inhibitor I kappa B, we studied a potential inhibition of this pathway by acetylsalicylate (aspirin) in human umbilical vein endothelial cells (HUVECs). METHODS AND RESULTS: Gel-shift analyses demonstrated dose-dependent inhibition of TNF-induced NF-kappa B mobilization by aspirin at concentrations ranging from 1 to 10 mmol/L. Induction of VCAM-1 and E-selectin surface expression by TNF was dose-dependently reduced by aspirin over the same range, while induction of intercellular adhesion molecule-1 (ICAM-1) was hardly affected. Aspirin appeared to prevent VCAM-1 transcription, since it dose-dependently inhibited induction of VCAM-1 mRNA by TNF. As a functional consequence, adhesion of U937 monocytes to TNF-stimulated HUVECs was markedly reduced by aspirin due to suppression of VCAM-1 and E-selectin upregulation. These effects of aspirin were not related to the inhibition of cyclooxygenase activity, since indomethacin was ineffective. CONCLUSIONS: Our data suggest that aspirin inhibits NF-kappa B mobilization, induction of VCAM-1 and E-selectin, and subsequent monocyte adhesion in endothelial cells stimulated by TNF, thereby providing an additional mechanism for therapeutic effects of aspirin." ], "offsets": [ [ 114, 1649 ] ] } ]

[ { "id": "2091", "type": "other_organic_compound", "text": [ "Aspirin" ], "offsets": [ [ 0, 7 ] ], "normalized": [] }, { "id": "2092", "type": "other_name", "text": [ "nuclear factor-kappa B mobilization" ], "offsets": [ [ 17, 52 ] ], "normalized": [] }, { "id": "2093", "type": "protein_molecule", "text": [ "nuclear factor-kappa B" ], "offsets": [ [ 17, 39 ] ], "normalized": [] }, { "id": "2094", "type": "other_name", "text": [ "monocyte adhesion" ], "offsets": [ [ 57, 74 ] ], "normalized": [] }, { "id": "2095", "type": "cell_line", "text": [ "stimulated human endothelial cells" ], "offsets": [ [ 78, 112 ] ], "normalized": [] }, { "id": "2096", "type": "protein_molecule", "text": [ "vascular cell adhesion molecule-1" ], "offsets": [ [ 143, 176 ] ], "normalized": [] }, { "id": "2097", "type": "protein_molecule", "text": [ "VCAM-1" ], "offsets": [ [ 178, 184 ] ], "normalized": [] }, { "id": "2098", "type": "protein_molecule", "text": [ "E-selectin" ], "offsets": [ [ 190, 200 ] ], "normalized": [] }, { "id": "2099", "type": "protein_molecule", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 204, 231 ] ], "normalized": [] }, { "id": "2100", "type": "protein_molecule", "text": [ "TNF" ], "offsets": [ [ 233, 236 ] ], "normalized": [] }, { "id": "2101", "type": "protein_family_or_group", "text": [ "transcription factor" ], "offsets": [ [ 273, 293 ] ], "normalized": [] }, { "id": "2102", "type": "protein_molecule", "text": [ "nuclear factor-kappa B" ], "offsets": [ [ 294, 316 ] ], "normalized": [] }, { "id": "2103", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 318, 328 ] ], "normalized": [] }, { "id": "2104", "type": "other_organic_compound", "text": [ "salicylates" ], "offsets": [ [ 337, 348 ] ], "normalized": [] }, { "id": "2105", "type": "other_name", "text": [ "NF-kappa B activation" ], "offsets": [ [ 379, 400 ] ], "normalized": [] }, { "id": "2106", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 379, 389 ] ], "normalized": [] }, { "id": "2107", "type": "protein_molecule", "text": [ "I kappa B" ], "offsets": [ [ 448, 457 ] ], "normalized": [] }, { "id": "2108", "type": "other_organic_compound", "text": [ "acetylsalicylate" ], "offsets": [ [ 512, 528 ] ], "normalized": [] }, { "id": "2109", "type": "other_organic_compound", "text": [ "aspirin" ], "offsets": [ [ 530, 537 ] ], "normalized": [] }, { "id": "2110", "type": "cell_line", "text": [ "human umbilical vein endothelial cells" ], "offsets": [ [ 542, 580 ] ], "normalized": [] }, { "id": "2111", "type": "cell_line", "text": [ "HUVECs" ], "offsets": [ [ 582, 588 ] ], "normalized": [] }, { "id": "2112", "type": "other_name", "text": [ "Gel-shift analyses" ], "offsets": [ [ 612, 630 ] ], "normalized": [] }, { "id": "2113", "type": "other_name", "text": [ "dose-dependent inhibition" ], "offsets": [ [ 644, 669 ] ], "normalized": [] }, { "id": "2114", "type": "other_name", "text": [ "TNF-induced NF-kappa B mobilization" ], "offsets": [ [ 673, 708 ] ], "normalized": [] }, { "id": "2115", "type": "protein_molecule", "text": [ "TNF" ], "offsets": [ [ 673, 676 ] ], "normalized": [] }, { "id": "2116", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 685, 695 ] ], "normalized": [] }, { "id": "2117", "type": "other_organic_compound", "text": [ "aspirin" ], "offsets": [ [ 712, 719 ] ], "normalized": [] }, { "id": "2118", "type": "protein_molecule", "text": [ "VCAM-1" ], "offsets": [ [ 780, 786 ] ], "normalized": [] }, { "id": "2119", "type": "other_name", "text": [ "E-selectin surface expression" ], "offsets": [ [ 791, 820 ] ], "normalized": [] }, { "id": "2120", "type": "protein_molecule", "text": [ "E-selectin" ], "offsets": [ [ 791, 801 ] ], "normalized": [] }, { "id": "2121", "type": "protein_molecule", "text": [ "TNF" ], "offsets": [ [ 824, 827 ] ], "normalized": [] }, { "id": "2122", "type": "other_organic_compound", "text": [ "aspirin" ], "offsets": [ [ 860, 867 ] ], "normalized": [] }, { "id": "2123", "type": "protein_molecule", "text": [ "intercellular adhesion molecule-1" ], "offsets": [ [ 908, 941 ] ], "normalized": [] }, { "id": "2124", "type": "protein_molecule", "text": [ "ICAM-1" ], "offsets": [ [ 943, 949 ] ], "normalized": [] }, { "id": "2125", "type": "other_organic_compound", "text": [ "Aspirin" ], "offsets": [ [ 972, 979 ] ], "normalized": [] }, { "id": "2126", "type": "other_name", "text": [ "VCAM-1 transcription" ], "offsets": [ [ 1000, 1020 ] ], "normalized": [] }, { "id": "2127", "type": "protein_molecule", "text": [ "VCAM-1" ], "offsets": [ [ 1000, 1006 ] ], "normalized": [] }, { "id": "2128", "type": "RNA_molecule", "text": [ "VCAM-1 mRNA" ], "offsets": [ [ 1071, 1082 ] ], "normalized": [] }, { "id": "2129", "type": "protein_molecule", "text": [ "VCAM-1" ], "offsets": [ [ 1071, 1077 ] ], "normalized": [] }, { "id": "2130", "type": "protein_molecule", "text": [ "TNF" ], "offsets": [ [ 1086, 1089 ] ], "normalized": [] }, { "id": "2131", "type": "cell_line", "text": [ "U937 monocytes" ], "offsets": [ [ 1132, 1146 ] ], "normalized": [] }, { "id": "2132", "type": "cell_line", "text": [ "TNF-stimulated HUVECs" ], "offsets": [ [ 1150, 1171 ] ], "normalized": [] }, { "id": "2133", "type": "protein_molecule", "text": [ "TNF" ], "offsets": [ [ 1150, 1153 ] ], "normalized": [] }, { "id": "2134", "type": "cell_line", "text": [ "HUVECs" ], "offsets": [ [ 1165, 1171 ] ], "normalized": [] }, { "id": "2135", "type": "other_organic_compound", "text": [ "aspirin" ], "offsets": [ [ 1196, 1203 ] ], "normalized": [] }, { "id": "2136", "type": "other_name", "text": [ "VCAM-1 and E-selectin upregulation" ], "offsets": [ [ 1226, 1260 ] ], "normalized": [] }, { "id": "2137", "type": "other_name", "text": [ "VCAM-1" ], "offsets": [ [ 1226, 1232 ] ], "normalized": [] }, { "id": "2138", "type": "protein_molecule", "text": [ "VCAM-1" ], "offsets": [ [ 1226, 1232 ] ], "normalized": [] }, { "id": "2139", "type": "other_name", "text": [ "E-selectin upregulation" ], "offsets": [ [ 1237, 1260 ] ], "normalized": [] }, { "id": "2140", "type": "protein_molecule", "text": [ "E-selectin" ], "offsets": [ [ 1237, 1247 ] ], "normalized": [] }, { "id": "2141", "type": "other_organic_compound", "text": [ "aspirin" ], "offsets": [ [ 1279, 1286 ] ], "normalized": [] }, { "id": "2142", "type": "other_name", "text": [ "cyclooxygenase activity" ], "offsets": [ [ 1325, 1348 ] ], "normalized": [] }, { "id": "2143", "type": "protein_molecule", "text": [ "cyclooxygenase" ], "offsets": [ [ 1325, 1339 ] ], "normalized": [] }, { "id": "2144", "type": "other_organic_compound", "text": [ "indomethacin" ], "offsets": [ [ 1356, 1368 ] ], "normalized": [] }, { "id": "2145", "type": "other_organic_compound", "text": [ "aspirin" ], "offsets": [ [ 1421, 1428 ] ], "normalized": [] }, { "id": "2146", "type": "other_organic_compound", "text": [ "NF-kappa B mobilization" ], "offsets": [ [ 1438, 1461 ] ], "normalized": [] }, { "id": "2147", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 1438, 1448 ] ], "normalized": [] }, { "id": "2148", "type": "protein_molecule", "text": [ "VCAM-1" ], "offsets": [ [ 1476, 1482 ] ], "normalized": [] }, { "id": "2149", "type": "protein_molecule", "text": [ "E-selectin" ], "offsets": [ [ 1487, 1497 ] ], "normalized": [] }, { "id": "2150", "type": "other_name", "text": [ "monocyte adhesion" ], "offsets": [ [ 1514, 1531 ] ], "normalized": [] }, { "id": "2151", "type": "cell_type", "text": [ "endothelial cells" ], "offsets": [ [ 1535, 1552 ] ], "normalized": [] }, { "id": "2152", "type": "protein_molecule", "text": [ "TNF" ], "offsets": [ [ 1567, 1570 ] ], "normalized": [] }, { "id": "2153", "type": "other_name", "text": [ "therapeutic effects" ], "offsets": [ [ 1618, 1637 ] ], "normalized": [] }, { "id": "2154", "type": "other_organic_compound", "text": [ "aspirin" ], "offsets": [ [ 1641, 1648 ] ], "normalized": [] } ]

[]

[]

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[ { "id": "2156", "type": "title", "text": [ "Activation of NF-kappa B by phosphatase inhibitors involves the phosphorylation of I kappa B alpha at phosphatase 2A-sensitive sites." ], "offsets": [ [ 0, 133 ] ] }, { "id": "2157", "type": "abstract", "text": [ "Activation of NF-kappa B by various cellular stimuli involves the phosphorylation and subsequent degradation of its inhibitor, I kappa B alpha, although the underlying mechanism remains unclear. In the present study, the role of serine/threonine phosphatases in the regulation of I kappa B alpha phosphorylation was investigated. Our studies demonstrate that incubation of human T cells with low concentrations (approximately 1-5 nM) of calyculin A or okadaic acid, potent inhibitors of protein phosphatase type 1 (PP-1) and type 2A (PP-2A), induces the phosphorylation of I kappa B alpha even in the absence of any cellular stimulus. This action of the phosphatase inhibitors, which is associated with the activation of the RelA.p50 NF-kappa B heterodimer, is not affected by agents that block the induction of I kappa B alpha phosphorylation by tumor necrosis factor alpha (TNF-alpha). Furthermore, the phosphorylated I kappa B alpha from calyculin A-treated cells, but not that from TNF-alpha-stimulated cells, is sensitive to PP-2A in vitro, suggesting the existence of fundamental differences in the phosphorylation of I kappa B alpha induced by the two different NF-kappa B inducers. However, induction of I kappa B alpha phosphorylation by both TNF-alpha and the phosphatase inhibitors is associated with the subsequent degradation of I kappa B alpha. We further demonstrate that TNF-alpha- and calyculin A-induced I kappa B alpha degradation exhibits similar but not identical sensitivities to a proteasome inhibitor. Together, these results suggest that phosphorylation of I kappa B alpha, mediated through both the TNF-alpha-inducible and the PP-2A-opposing kinases, may serve to target I kappa B alpha for proteasome-mediated degradation." ], "offsets": [ [ 134, 1883 ] ] } ]

[ { "id": "2158", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 14, 24 ] ], "normalized": [] }, { "id": "2159", "type": "other_name", "text": [ "phosphatase inhibitors" ], "offsets": [ [ 28, 50 ] ], "normalized": [] }, { "id": "2160", "type": "protein_family_or_group", "text": [ "phosphatase" ], "offsets": [ [ 28, 39 ] ], "normalized": [] }, { "id": "2161", "type": "other_name", "text": [ "phosphorylation" ], "offsets": [ [ 64, 79 ] ], "normalized": [] }, { "id": "2162", "type": "protein_molecule", "text": [ "I kappa B alpha" ], "offsets": [ [ 83, 98 ] ], "normalized": [] }, { "id": "2163", "type": "protein_domain_or_region", "text": [ "phosphatase 2A-sensitive sites" ], "offsets": [ [ 102, 132 ] ], "normalized": [] }, { "id": "2164", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 148, 158 ] ], "normalized": [] }, { "id": "2165", "type": "other_name", "text": [ "cellular stimuli" ], "offsets": [ [ 170, 186 ] ], "normalized": [] }, { "id": "2166", "type": "other_name", "text": [ "phosphorylation" ], "offsets": [ [ 200, 215 ] ], "normalized": [] }, { "id": "2167", "type": "other_name", "text": [ "inhibitor," ], "offsets": [ [ 250, 260 ] ], "normalized": [] }, { "id": "2168", "type": "protein_molecule", "text": [ "I kappa B alpha" ], "offsets": [ [ 261, 276 ] ], "normalized": [] }, { "id": "2169", "type": "protein_molecule", "text": [ "serine/threonine phosphatases" ], "offsets": [ [ 363, 392 ] ], "normalized": [] }, { "id": "2170", "type": "other_name", "text": [ "I kappa B alpha phosphorylation" ], "offsets": [ [ 414, 445 ] ], "normalized": [] }, { "id": "2171", "type": "protein_molecule", "text": [ "I kappa B alpha" ], "offsets": [ [ 414, 429 ] ], "normalized": [] }, { "id": "2172", "type": "cell_type", "text": [ "human T cells" ], "offsets": [ [ 507, 520 ] ], "normalized": [] }, { "id": "2173", "type": "other_organic_compound", "text": [ "calyculin A" ], "offsets": [ [ 571, 582 ] ], "normalized": [] }, { "id": "2174", "type": "other_organic_compound", "text": [ "okadaic acid" ], "offsets": [ [ 586, 598 ] ], "normalized": [] }, { "id": "2175", "type": "(AND protein_family_or_group protein_family_or_group)", "text": [ "protein phosphatase type 1 (PP-1) and type 2A" ], "offsets": [ [ 621, 666 ] ], "normalized": [] }, { "id": "2176", "type": "", "text": [ "protein phosphatase" ], "offsets": [ [ 621, 640 ] ], "normalized": [] }, { "id": "2177", "type": "", "text": [ "type 1 (PP-1)" ], "offsets": [ [ 641, 654 ] ], "normalized": [] }, { "id": "2178", "type": "", "text": [ "type 2A" ], "offsets": [ [ 659, 666 ] ], "normalized": [] }, { "id": "2179", "type": "protein_family_or_group", "text": [ "PP-2A" ], "offsets": [ [ 668, 673 ] ], "normalized": [] }, { "id": "2180", "type": "other_name", "text": [ "phosphorylation" ], "offsets": [ [ 688, 703 ] ], "normalized": [] }, { "id": "2181", "type": "protein_molecule", "text": [ "I kappa B alpha" ], "offsets": [ [ 707, 722 ] ], "normalized": [] }, { "id": "2182", "type": "other_organic_compound", "text": [ "phosphatase inhibitors" ], "offsets": [ [ 788, 810 ] ], "normalized": [] }, { "id": "2183", "type": "protein_complex", "text": [ "RelA.p50 NF-kappa B heterodimer" ], "offsets": [ [ 859, 890 ] ], "normalized": [] }, { "id": "2184", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 868, 878 ] ], "normalized": [] }, { "id": "2185", "type": "other_name", "text": [ "I kappa B alpha phosphorylation" ], "offsets": [ [ 946, 977 ] ], "normalized": [] }, { "id": "2186", "type": "protein_molecule", "text": [ "I kappa B alpha" ], "offsets": [ [ 946, 961 ] ], "normalized": [] }, { "id": "2187", "type": "protein_molecule", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 981, 1008 ] ], "normalized": [] }, { "id": "2188", "type": "protein_molecule", "text": [ "TNF-alpha" ], "offsets": [ [ 1010, 1019 ] ], "normalized": [] }, { "id": "2189", "type": "protein_molecule", "text": [ "phosphorylated I kappa B alpha" ], "offsets": [ [ 1039, 1069 ] ], "normalized": [] }, { "id": "2190", "type": "protein_molecule", "text": [ "I kappa B alpha" ], "offsets": [ [ 1054, 1069 ] ], "normalized": [] }, { "id": "2191", "type": "cell_line", "text": [ "calyculin A-treated cells" ], "offsets": [ [ 1075, 1100 ] ], "normalized": [] }, { "id": "2192", "type": "other_organic_compound", "text": [ "calyculin A" ], "offsets": [ [ 1075, 1086 ] ], "normalized": [] }, { "id": "2193", "type": "cell_line", "text": [ "TNF-alpha-stimulated cells" ], "offsets": [ [ 1120, 1146 ] ], "normalized": [] }, { "id": "2194", "type": "protein_molecule", "text": [ "TNF-alpha" ], "offsets": [ [ 1120, 1129 ] ], "normalized": [] }, { "id": "2195", "type": "protein_family_or_group", "text": [ "PP-2A" ], "offsets": [ [ 1164, 1169 ] ], "normalized": [] }, { "id": "2196", "type": "other_name", "text": [ "phosphorylation" ], "offsets": [ [ 1239, 1254 ] ], "normalized": [] }, { "id": "2197", "type": "protein_molecule", "text": [ "I kappa B alpha" ], "offsets": [ [ 1258, 1273 ] ], "normalized": [] }, { "id": "2198", "type": "other_name", "text": [ "NF-kappa B inducers" ], "offsets": [ [ 1303, 1322 ] ], "normalized": [] }, { "id": "2199", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 1303, 1313 ] ], "normalized": [] }, { "id": "2200", "type": "other_name", "text": [ "I kappa B alpha phosphorylation" ], "offsets": [ [ 1346, 1377 ] ], "normalized": [] }, { "id": "2201", "type": "protein_molecule", "text": [ "I kappa B alpha" ], "offsets": [ [ 1346, 1361 ] ], "normalized": [] }, { "id": "2202", "type": "protein_molecule", "text": [ "TNF-alpha" ], "offsets": [ [ 1386, 1395 ] ], "normalized": [] }, { "id": "2203", "type": "other_organic_compound", "text": [ "phosphatase inhibitors" ], "offsets": [ [ 1404, 1426 ] ], "normalized": [] }, { "id": "2204", "type": "protein_molecule", "text": [ "I kappa B alpha" ], "offsets": [ [ 1476, 1491 ] ], "normalized": [] }, { "id": "2205", "type": "(AND other_name other_name)", "text": [ "TNF-alpha- and calyculin A-induced I kappa B alpha degradation" ], "offsets": [ [ 1521, 1583 ] ], "normalized": [] }, { "id": "2206", "type": "", "text": [ "TNF-alpha-" ], "offsets": [ [ 1521, 1531 ] ], "normalized": [] }, { "id": "2207", "type": "", "text": [ "calyculin A-induced I kappa B alpha" ], "offsets": [ [ 1536, 1571 ] ], "normalized": [] }, { "id": "2208", "type": "", "text": [ "degradation" ], "offsets": [ [ 1572, 1583 ] ], "normalized": [] }, { "id": "2209", "type": "other_organic_compound", "text": [ "proteasome inhibitor" ], "offsets": [ [ 1638, 1658 ] ], "normalized": [] }, { "id": "2210", "type": "other_name", "text": [ "phosphorylation" ], "offsets": [ [ 1697, 1712 ] ], "normalized": [] }, { "id": "2211", "type": "protein_molecule", "text": [ "I kappa B alpha" ], "offsets": [ [ 1716, 1731 ] ], "normalized": [] }, { "id": "2212", "type": "protein_molecule", "text": [ "TNF-alpha" ], "offsets": [ [ 1759, 1768 ] ], "normalized": [] }, { "id": "2213", "type": "protein_family_or_group", "text": [ "PP-2A-opposing kinases" ], "offsets": [ [ 1787, 1809 ] ], "normalized": [] }, { "id": "2214", "type": "protein_family_or_group", "text": [ "PP-2A" ], "offsets": [ [ 1787, 1792 ] ], "normalized": [] }, { "id": "2215", "type": "protein_molecule", "text": [ "I kappa B alpha" ], "offsets": [ [ 1831, 1846 ] ], "normalized": [] }, { "id": "2216", "type": "other_name", "text": [ "proteasome-mediated degradation" ], "offsets": [ [ 1851, 1882 ] ], "normalized": [] }, { "id": "2217", "type": "protein_complex", "text": [ "proteasome" ], "offsets": [ [ 1851, 1861 ] ], "normalized": [] } ]

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[]

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[ { "id": "2219", "type": "title", "text": [ "Sp1 functions in a chromatin-dependent manner to augment human alpha-globin promoter activity." ], "offsets": [ [ 0, 94 ] ] }, { "id": "2220", "type": "abstract", "text": [ "The 5' flanking region of the human alpha-globin gene is highly G + C rich and contains multiple copies of the consensus sequence for the Sp1 binding site. We investigated the role of this G + C-rich region in augmenting alpha-globin promoter activity in the presence of the far-upstream alpha-globin enhancer, HS-40. We show that in transiently transfected erythroid cells, deletion of the alpha-globin G + C-rich 5' flanking region has no effect on alpha-globin promoter activity. However, upon stable integration into chromatin, deletion of this region causes a nearly 90% decrease in promoter activity compared with expression from an alpha-globin promoter retaining this region. These results suggest that the alpha-globin G + C-rich 5' flanking region augments alpha-globin promoter activity in a chromatin-dependent manner. We further show that this G + C-rich region is required for the activation of alpha-globin gene expression during erythroid differentiation. Finally, we show by both footprint analysis and functional assays that the ability of the G + C-rich region to increase alpha-globin promoter activity from a stably integrated alpha-globin gene is mediated by its multiple binding sites for the transcription factor Sp1." ], "offsets": [ [ 95, 1336 ] ] } ]

[ { "id": "2221", "type": "other_name", "text": [ "Sp1 functions" ], "offsets": [ [ 0, 13 ] ], "normalized": [] }, { "id": "2222", "type": "protein_molecule", "text": [ "Sp1" ], "offsets": [ [ 0, 3 ] ], "normalized": [] }, { "id": "2223", "type": "other_name", "text": [ "chromatin-dependent manner" ], "offsets": [ [ 19, 45 ] ], "normalized": [] }, { "id": "2224", "type": "DNA_family_or_group", "text": [ "chromatin" ], "offsets": [ [ 19, 28 ] ], "normalized": [] }, { "id": "2225", "type": "other_name", "text": [ "human alpha-globin promoter activity" ], "offsets": [ [ 57, 93 ] ], "normalized": [] }, { "id": "2226", "type": "DNA_domain_or_region", "text": [ "human alpha-globin promoter" ], "offsets": [ [ 57, 84 ] ], "normalized": [] }, { "id": "2227", "type": "DNA_domain_or_region", "text": [ "5' flanking region" ], "offsets": [ [ 99, 117 ] ], "normalized": [] }, { "id": "2228", "type": "DNA_domain_or_region", "text": [ "human alpha-globin gene" ], "offsets": [ [ 125, 148 ] ], "normalized": [] }, { "id": "2229", "type": "DNA_N/A", "text": [ "G + C rich" ], "offsets": [ [ 159, 169 ] ], "normalized": [] }, { "id": "2230", "type": "DNA_domain_or_region", "text": [ "consensus sequence" ], "offsets": [ [ 206, 224 ] ], "normalized": [] }, { "id": "2231", "type": "DNA_domain_or_region", "text": [ "Sp1 binding site" ], "offsets": [ [ 233, 249 ] ], "normalized": [] }, { "id": "2232", "type": "protein_molecule", "text": [ "Sp1" ], "offsets": [ [ 233, 236 ] ], "normalized": [] }, { "id": "2233", "type": "DNA_domain_or_region", "text": [ "G + C-rich region" ], "offsets": [ [ 284, 301 ] ], "normalized": [] }, { "id": "2234", "type": "other_name", "text": [ "alpha-globin promoter activity" ], "offsets": [ [ 316, 346 ] ], "normalized": [] }, { "id": "2235", "type": "DNA_domain_or_region", "text": [ "alpha-globin promoter" ], "offsets": [ [ 316, 337 ] ], "normalized": [] }, { "id": "2236", "type": "DNA_domain_or_region", "text": [ "far-upstream alpha-globin enhancer" ], "offsets": [ [ 370, 404 ] ], "normalized": [] }, { "id": "2237", "type": "DNA_domain_or_region", "text": [ "HS-40" ], "offsets": [ [ 406, 411 ] ], "normalized": [] }, { "id": "2238", "type": "cell_line", "text": [ "transiently transfected erythroid cells" ], "offsets": [ [ 429, 468 ] ], "normalized": [] }, { "id": "2239", "type": "DNA_domain_or_region", "text": [ "alpha-globin G + C-rich 5' flanking region" ], "offsets": [ [ 486, 528 ] ], "normalized": [] }, { "id": "2240", "type": "other_name", "text": [ "alpha-globin promoter activity" ], "offsets": [ [ 546, 576 ] ], "normalized": [] }, { "id": "2241", "type": "DNA_domain_or_region", "text": [ "alpha-globin promoter" ], "offsets": [ [ 546, 567 ] ], "normalized": [] }, { "id": "2242", "type": "DNA_family_or_group", "text": [ "chromatin" ], "offsets": [ [ 616, 625 ] ], "normalized": [] }, { "id": "2243", "type": "other_name", "text": [ "promoter activity" ], "offsets": [ [ 683, 700 ] ], "normalized": [] }, { "id": "2244", "type": "DNA_domain_or_region", "text": [ "alpha-globin promoter" ], "offsets": [ [ 734, 755 ] ], "normalized": [] }, { "id": "2245", "type": "DNA_domain_or_region", "text": [ "alpha-globin G + C-rich 5' flanking region" ], "offsets": [ [ 810, 852 ] ], "normalized": [] }, { "id": "2246", "type": "other_name", "text": [ "alpha-globin promoter activity" ], "offsets": [ [ 862, 892 ] ], "normalized": [] }, { "id": "2247", "type": "DNA_domain_or_region", "text": [ "alpha-globin promoter" ], "offsets": [ [ 862, 883 ] ], "normalized": [] }, { "id": "2248", "type": "other_name", "text": [ "chromatin-dependent manner" ], "offsets": [ [ 898, 924 ] ], "normalized": [] }, { "id": "2249", "type": "DNA_family_or_group", "text": [ "chromatin" ], "offsets": [ [ 898, 907 ] ], "normalized": [] }, { "id": "2250", "type": "DNA_domain_or_region", "text": [ "G + C-rich region" ], "offsets": [ [ 952, 969 ] ], "normalized": [] }, { "id": "2251", "type": "other_name", "text": [ "alpha-globin gene expression" ], "offsets": [ [ 1004, 1032 ] ], "normalized": [] }, { "id": "2252", "type": "DNA_domain_or_region", "text": [ "alpha-globin gene" ], "offsets": [ [ 1004, 1021 ] ], "normalized": [] }, { "id": "2253", "type": "other_name", "text": [ "erythroid differentiation" ], "offsets": [ [ 1040, 1065 ] ], "normalized": [] }, { "id": "2254", "type": "other_name", "text": [ "footprint analysis" ], "offsets": [ [ 1092, 1110 ] ], "normalized": [] }, { "id": "2255", "type": "other_name", "text": [ "functional assays" ], "offsets": [ [ 1115, 1132 ] ], "normalized": [] }, { "id": "2256", "type": "DNA_domain_or_region", "text": [ "G + C-rich region" ], "offsets": [ [ 1157, 1174 ] ], "normalized": [] }, { "id": "2257", "type": "other_name", "text": [ "alpha-globin promoter activity" ], "offsets": [ [ 1187, 1217 ] ], "normalized": [] }, { "id": "2258", "type": "DNA_domain_or_region", "text": [ "alpha-globin promoter" ], "offsets": [ [ 1187, 1208 ] ], "normalized": [] }, { "id": "2259", "type": "DNA_domain_or_region", "text": [ "alpha-globin gene" ], "offsets": [ [ 1243, 1260 ] ], "normalized": [] }, { "id": "2260", "type": "DNA_domain_or_region", "text": [ "multiple binding sites" ], "offsets": [ [ 1280, 1302 ] ], "normalized": [] }, { "id": "2261", "type": "protein_family_or_group", "text": [ "transcription factor" ], "offsets": [ [ 1311, 1331 ] ], "normalized": [] }, { "id": "2262", "type": "protein_molecule", "text": [ "Sp1" ], "offsets": [ [ 1332, 1335 ] ], "normalized": [] } ]

[]

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[ { "id": "2264", "type": "title", "text": [ "Costimulation of human CD4+ T cells with LFA-3 and B7 induce distinct effects on AP-1 and NF-kappa B transcription factors." ], "offsets": [ [ 0, 123 ] ] }, { "id": "2265", "type": "abstract", "text": [ "We have earlier shown that stimulation of human CD4+ T cells with SEA presented on Chinese hamster ovary (CHO)-DR transfectants coexpressing either B7 or LFA-3 resulted in distinct cytokine profiles. We now demonstrate that B7, but not LFA-3, strongly costimulated IL-2 transcription and mRNA expression in CD4+ T cells. Maximal increase in IL-2 transcription was recorded with CHO-DR/B7/LFA-3, suggesting a cooperative effect of B7 and LFA-3 at the transcriptional level. Gel-shift analysis demonstrated that stimulation of CD4+ T cells with CHO-DR and staphylococcal enterotoxin A was sufficient to induce significant amounts of NF-kappa B binding proteins, whereas induction of AP-1 binding proteins required costimulation. LFA-3 induced moderate levels of AP-1, but did not influence the levels of NF-kappa B, while B7 costimulation strongly induced both AP-1 and substantially enhanced NF-kappa B binding proteins. The CHO-DR/B7/LFA-3 triple transfectant induced a further increase in AP-1 and NF-kappa B binding proteins compared with the double transfectants. The level of Oct-1 binding proteins remained similar in all samples. Super-shift analysis revealed that the NF-kappa B complex of costimulated CD4+ T cells contained large amounts of p50, substantial amounts of p65, and marginal levels of c-Rel proteins. The AP-1 binding proteins contained c-Jun, Jun-D, and Fra-1, but marginal amounts of Jun-B and c-Fos. Our results indicate distinct effects of B7 and LFA-3 costimulation on the activity of AP-1 and NF-kappa B. These may partly account for the differential effects of B7 and LFA-3 costimulation on IL-2 expression." ], "offsets": [ [ 124, 1759 ] ] } ]

[ { "id": "2266", "type": "cell_line", "text": [ "human CD4+ T cells" ], "offsets": [ [ 17, 35 ] ], "normalized": [] }, { "id": "2267", "type": "protein_molecule", "text": [ "LFA-3" ], "offsets": [ [ 41, 46 ] ], "normalized": [] }, { "id": "2268", "type": "protein_molecule", "text": [ "B7" ], "offsets": [ [ 51, 53 ] ], "normalized": [] }, { "id": "2269", "type": "protein_N/A", "text": [ "AP-1" ], "offsets": [ [ 81, 85 ] ], "normalized": [] }, { "id": "2270", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 90, 100 ] ], "normalized": [] }, { "id": "2271", "type": "protein_family_or_group", "text": [ "transcription factors" ], "offsets": [ [ 101, 122 ] ], "normalized": [] }, { "id": "2272", "type": "cell_line", "text": [ "human CD4+ T cells" ], "offsets": [ [ 166, 184 ] ], "normalized": [] }, { "id": "2273", "type": "cell_line", "text": [ "Chinese hamster ovary (CHO)-DR transfectants" ], "offsets": [ [ 207, 251 ] ], "normalized": [] }, { "id": "2274", "type": "body_part", "text": [ "Chinese hamster ovary" ], "offsets": [ [ 207, 228 ] ], "normalized": [] }, { "id": "2275", "type": "multi_cell", "text": [ "hamster" ], "offsets": [ [ 215, 222 ] ], "normalized": [] }, { "id": "2276", "type": "protein_molecule", "text": [ "B7" ], "offsets": [ [ 272, 274 ] ], "normalized": [] }, { "id": "2277", "type": "protein_molecule", "text": [ "LFA-3" ], "offsets": [ [ 278, 283 ] ], "normalized": [] }, { "id": "2278", "type": "other_name", "text": [ "cytokine profiles" ], "offsets": [ [ 305, 322 ] ], "normalized": [] }, { "id": "2279", "type": "protein_family_or_group", "text": [ "cytokine" ], "offsets": [ [ 305, 313 ] ], "normalized": [] }, { "id": "2280", "type": "protein_molecule", "text": [ "B7" ], "offsets": [ [ 348, 350 ] ], "normalized": [] }, { "id": "2281", "type": "protein_molecule", "text": [ "LFA-3" ], "offsets": [ [ 360, 365 ] ], "normalized": [] }, { "id": "2282", "type": "other_name", "text": [ "IL-2 transcription" ], "offsets": [ [ 389, 407 ] ], "normalized": [] }, { "id": "2283", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 389, 393 ] ], "normalized": [] }, { "id": "2284", "type": "other_name", "text": [ "mRNA expression" ], "offsets": [ [ 412, 427 ] ], "normalized": [] }, { "id": "2285", "type": "cell_line", "text": [ "CD4+ T cells" ], "offsets": [ [ 431, 443 ] ], "normalized": [] }, { "id": "2286", "type": "other_name", "text": [ "IL-2 transcription" ], "offsets": [ [ 465, 483 ] ], "normalized": [] }, { "id": "2287", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 465, 469 ] ], "normalized": [] }, { "id": "2288", "type": "protein_molecule", "text": [ "CHO-DR/B7/LFA-3" ], "offsets": [ [ 502, 517 ] ], "normalized": [] }, { "id": "2289", "type": "protein_molecule", "text": [ "B7" ], "offsets": [ [ 509, 511 ] ], "normalized": [] }, { "id": "2290", "type": "protein_molecule", "text": [ "LFA-3" ], "offsets": [ [ 512, 517 ] ], "normalized": [] }, { "id": "2291", "type": "other_name", "text": [ "cooperative effect" ], "offsets": [ [ 532, 550 ] ], "normalized": [] }, { "id": "2292", "type": "protein_molecule", "text": [ "B7" ], "offsets": [ [ 554, 556 ] ], "normalized": [] }, { "id": "2293", "type": "protein_molecule", "text": [ "LFA-3" ], "offsets": [ [ 561, 566 ] ], "normalized": [] }, { "id": "2294", "type": "cell_line", "text": [ "CD4+ T cells" ], "offsets": [ [ 649, 661 ] ], "normalized": [] }, { "id": "2295", "type": "protein_molecule", "text": [ "CHO-DR" ], "offsets": [ [ 667, 673 ] ], "normalized": [] }, { "id": "2296", "type": "other_organic_compound", "text": [ "staphylococcal enterotoxin A" ], "offsets": [ [ 678, 706 ] ], "normalized": [] }, { "id": "2297", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 755, 765 ] ], "normalized": [] }, { "id": "2298", "type": "protein_family_or_group", "text": [ "AP-1 binding proteins" ], "offsets": [ [ 805, 826 ] ], "normalized": [] }, { "id": "2299", "type": "protein_molecule", "text": [ "LFA-3" ], "offsets": [ [ 851, 856 ] ], "normalized": [] }, { "id": "2300", "type": "protein_molecule", "text": [ "AP-1" ], "offsets": [ [ 884, 888 ] ], "normalized": [] }, { "id": "2301", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 926, 936 ] ], "normalized": [] }, { "id": "2302", "type": "other_name", "text": [ "B7 costimulation" ], "offsets": [ [ 944, 960 ] ], "normalized": [] }, { "id": "2303", "type": "protein_molecule", "text": [ "B7" ], "offsets": [ [ 944, 946 ] ], "normalized": [] }, { "id": "2304", "type": "protein_molecule", "text": [ "AP-1" ], "offsets": [ [ 983, 987 ] ], "normalized": [] }, { "id": "2305", "type": "protein_family_or_group", "text": [ "NF-kappa B binding proteins" ], "offsets": [ [ 1015, 1042 ] ], "normalized": [] }, { "id": "2306", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 1015, 1025 ] ], "normalized": [] }, { "id": "2307", "type": "cell_line", "text": [ "CHO-DR/B7/LFA-3 triple transfectant" ], "offsets": [ [ 1048, 1083 ] ], "normalized": [] }, { "id": "2308", "type": "protein_molecule", "text": [ "B7" ], "offsets": [ [ 1055, 1057 ] ], "normalized": [] }, { "id": "2309", "type": "protein_molecule", "text": [ "LFA-3" ], "offsets": [ [ 1058, 1063 ] ], "normalized": [] }, { "id": "2310", "type": "protein_molecule", "text": [ "AP-1" ], "offsets": [ [ 1114, 1118 ] ], "normalized": [] }, { "id": "2311", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 1123, 1133 ] ], "normalized": [] }, { "id": "2312", "type": "protein_family_or_group", "text": [ "binding proteins" ], "offsets": [ [ 1134, 1150 ] ], "normalized": [] }, { "id": "2313", "type": "cell_line", "text": [ "double transfectants" ], "offsets": [ [ 1169, 1189 ] ], "normalized": [] }, { "id": "2314", "type": "protein_family_or_group", "text": [ "Oct-1 binding proteins" ], "offsets": [ [ 1204, 1226 ] ], "normalized": [] }, { "id": "2315", "type": "other_name", "text": [ "Super-shift analysis" ], "offsets": [ [ 1260, 1280 ] ], "normalized": [] }, { "id": "2316", "type": "protein_complex", "text": [ "NF-kappa B complex" ], "offsets": [ [ 1299, 1317 ] ], "normalized": [] }, { "id": "2317", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 1299, 1309 ] ], "normalized": [] }, { "id": "2318", "type": "cell_line", "text": [ "costimulated CD4+ T cells" ], "offsets": [ [ 1321, 1346 ] ], "normalized": [] }, { "id": "2319", "type": "cell_line", "text": [ "CD4+ T cells" ], "offsets": [ [ 1334, 1346 ] ], "normalized": [] }, { "id": "2320", "type": "protein_subunit", "text": [ "p50" ], "offsets": [ [ 1374, 1377 ] ], "normalized": [] }, { "id": "2321", "type": "protein_subunit", "text": [ "p65" ], "offsets": [ [ 1402, 1405 ] ], "normalized": [] }, { "id": "2322", "type": "protein_family_or_group", "text": [ "c-Rel proteins" ], "offsets": [ [ 1430, 1444 ] ], "normalized": [] }, { "id": "2323", "type": "protein_family_or_group", "text": [ "AP-1 binding proteins" ], "offsets": [ [ 1450, 1471 ] ], "normalized": [] }, { "id": "2324", "type": "protein_molecule", "text": [ "AP-1" ], "offsets": [ [ 1450, 1454 ] ], "normalized": [] }, { "id": "2325", "type": "protein_molecule", "text": [ "c-Jun" ], "offsets": [ [ 1482, 1487 ] ], "normalized": [] }, { "id": "2326", "type": "protein_molecule", "text": [ "Jun-D" ], "offsets": [ [ 1489, 1494 ] ], "normalized": [] }, { "id": "2327", "type": "protein_molecule", "text": [ "Fra-1" ], "offsets": [ [ 1500, 1505 ] ], "normalized": [] }, { "id": "2328", "type": "protein_molecule", "text": [ "Jun-B" ], "offsets": [ [ 1531, 1536 ] ], "normalized": [] }, { "id": "2329", "type": "protein_molecule", "text": [ "c-Fos" ], "offsets": [ [ 1541, 1546 ] ], "normalized": [] }, { "id": "2330", "type": "other_name", "text": [ "B7 and LFA-3 costimulation" ], "offsets": [ [ 1589, 1615 ] ], "normalized": [] }, { "id": "2331", "type": "protein_molecule", "text": [ "B7" ], "offsets": [ [ 1589, 1591 ] ], "normalized": [] }, { "id": "2332", "type": "protein_molecule", "text": [ "LFA-3" ], "offsets": [ [ 1596, 1601 ] ], "normalized": [] }, { "id": "2333", "type": "protein_molecule", "text": [ "AP-1" ], "offsets": [ [ 1635, 1639 ] ], "normalized": [] }, { "id": "2334", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 1644, 1654 ] ], "normalized": [] }, { "id": "2335", "type": "other_name", "text": [ "differential effects" ], "offsets": [ [ 1689, 1709 ] ], "normalized": [] }, { "id": "2336", "type": "other_name", "text": [ "B7 and LFA-3 costimulation" ], "offsets": [ [ 1713, 1739 ] ], "normalized": [] }, { "id": "2337", "type": "protein_molecule", "text": [ "B7" ], "offsets": [ [ 1713, 1715 ] ], "normalized": [] }, { "id": "2338", "type": "protein_molecule", "text": [ "LFA-3" ], "offsets": [ [ 1720, 1725 ] ], "normalized": [] }, { "id": "2339", "type": "other_name", "text": [ "IL-2 expression" ], "offsets": [ [ 1743, 1758 ] ], "normalized": [] }, { "id": "2340", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 1743, 1747 ] ], "normalized": [] } ]

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[ { "id": "2342", "type": "title", "text": [ "The Ah receptor recognizes DNA binding sites for the B cell transcription factor, BSAP: a possible mechanism for dioxin-mediated alteration of CD19 gene expression in human B lymphocytes." ], "offsets": [ [ 0, 187 ] ] }, { "id": "2343", "type": "abstract", "text": [ "2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) inhibits murine and human B lymphocyte immunoglobulin production through an unknown mechanism. This study investigated the effect of TCDD on expression of the CD19 gene in a human B lymphocyte cell line. Northern blot analysis showed that TCDD treatment decreased steady state levels of CD19 mRNA by 67% in the IM-9 cell line. Using a gel mobility shift assay, we identified a DNA-binding complex in IM-9 nuclear extracts that by several criteria appears to be the Ah receptor. In addition, the Ah receptor complex recognized a DNA binding site for B cell lineage-specific activator protein (BSAP) in the promoter region of the human CD19 gene which is similar to the consensus Ah receptor DNA binding site. These results suggest that the AhR could interfere with BSAP-stimulated CD19 gene transcription by competition for a common DNA binding site." ], "offsets": [ [ 188, 1080 ] ] } ]

[ { "id": "2344", "type": "protein_molecule", "text": [ "Ah receptor" ], "offsets": [ [ 4, 15 ] ], "normalized": [] }, { "id": "2345", "type": "DNA_domain_or_region", "text": [ "DNA binding sites" ], "offsets": [ [ 27, 44 ] ], "normalized": [] }, { "id": "2346", "type": "protein_family_or_group", "text": [ "B cell transcription factor" ], "offsets": [ [ 53, 80 ] ], "normalized": [] }, { "id": "2347", "type": "protein_family_or_group", "text": [ "transcription factor" ], "offsets": [ [ 60, 80 ] ], "normalized": [] }, { "id": "2348", "type": "protein_molecule", "text": [ "BSAP" ], "offsets": [ [ 82, 86 ] ], "normalized": [] }, { "id": "2349", "type": "other_name", "text": [ "dioxin-mediated alteration" ], "offsets": [ [ 113, 139 ] ], "normalized": [] }, { "id": "2350", "type": "other_name", "text": [ "CD19 gene expression" ], "offsets": [ [ 143, 163 ] ], "normalized": [] }, { "id": "2351", "type": "DNA_domain_or_region", "text": [ "CD19 gene" ], "offsets": [ [ 143, 152 ] ], "normalized": [] }, { "id": "2352", "type": "cell_type", "text": [ "human B lymphocytes" ], "offsets": [ [ 167, 186 ] ], "normalized": [] }, { "id": "2353", "type": "other_organic_compound", "text": [ "2,3,7,8-tetrachlorodibenzo-p-dioxin" ], "offsets": [ [ 188, 223 ] ], "normalized": [] }, { "id": "2354", "type": "other_organic_compound", "text": [ "TCDD" ], "offsets": [ [ 225, 229 ] ], "normalized": [] }, { "id": "2355", "type": "(AND other_name other_name)", "text": [ "murine and human B lymphocyte immunoglobulin production" ], "offsets": [ [ 240, 295 ] ], "normalized": [] }, { "id": "2356", "type": "", "text": [ "murine" ], "offsets": [ [ 240, 246 ] ], "normalized": [] }, { "id": "2357", "type": "", "text": [ "human" ], "offsets": [ [ 251, 256 ] ], "normalized": [] }, { "id": "2358", "type": "", "text": [ "B lymphocyte immunoglobulin production" ], "offsets": [ [ 257, 295 ] ], "normalized": [] }, { "id": "2359", "type": "other_organic_compound", "text": [ "TCDD" ], "offsets": [ [ 364, 368 ] ], "normalized": [] }, { "id": "2360", "type": "DNA_domain_or_region", "text": [ "CD19 gene" ], "offsets": [ [ 390, 399 ] ], "normalized": [] }, { "id": "2361", "type": "cell_line", "text": [ "human B lymphocyte cell line" ], "offsets": [ [ 405, 433 ] ], "normalized": [] }, { "id": "2362", "type": "other_name", "text": [ "Northern blot analysis" ], "offsets": [ [ 435, 457 ] ], "normalized": [] }, { "id": "2363", "type": "other_organic_compound", "text": [ "TCDD" ], "offsets": [ [ 470, 474 ] ], "normalized": [] }, { "id": "2364", "type": "RNA_molecule", "text": [ "CD19 mRNA" ], "offsets": [ [ 518, 527 ] ], "normalized": [] }, { "id": "2365", "type": "cell_line", "text": [ "IM-9 cell line" ], "offsets": [ [ 542, 556 ] ], "normalized": [] }, { "id": "2366", "type": "other_name", "text": [ "gel mobility shift assay" ], "offsets": [ [ 566, 590 ] ], "normalized": [] }, { "id": "2367", "type": "protein_complex", "text": [ "DNA-binding complex" ], "offsets": [ [ 608, 627 ] ], "normalized": [] }, { "id": "2368", "type": "cell_component", "text": [ "IM-9 nuclear extracts" ], "offsets": [ [ 631, 652 ] ], "normalized": [] }, { "id": "2369", "type": "protein_molecule", "text": [ "Ah receptor" ], "offsets": [ [ 696, 707 ] ], "normalized": [] }, { "id": "2370", "type": "protein_complex", "text": [ "Ah receptor complex" ], "offsets": [ [ 726, 745 ] ], "normalized": [] }, { "id": "2371", "type": "protein_molecule", "text": [ "Ah receptor" ], "offsets": [ [ 726, 737 ] ], "normalized": [] }, { "id": "2372", "type": "DNA_domain_or_region", "text": [ "DNA binding site" ], "offsets": [ [ 759, 775 ] ], "normalized": [] }, { "id": "2373", "type": "protein_family_or_group", "text": [ "B cell lineage-specific activator protein" ], "offsets": [ [ 780, 821 ] ], "normalized": [] }, { "id": "2374", "type": "protein_molecule", "text": [ "BSAP" ], "offsets": [ [ 823, 827 ] ], "normalized": [] }, { "id": "2375", "type": "DNA_domain_or_region", "text": [ "promoter region" ], "offsets": [ [ 836, 851 ] ], "normalized": [] }, { "id": "2376", "type": "DNA_domain_or_region", "text": [ "CD19 gene" ], "offsets": [ [ 865, 874 ] ], "normalized": [] }, { "id": "2377", "type": "DNA_domain_or_region", "text": [ "consensus Ah receptor DNA binding site" ], "offsets": [ [ 899, 937 ] ], "normalized": [] }, { "id": "2378", "type": "protein_molecule", "text": [ "Ah receptor" ], "offsets": [ [ 909, 920 ] ], "normalized": [] }, { "id": "2379", "type": "DNA_domain_or_region", "text": [ "DNA binding site" ], "offsets": [ [ 921, 937 ] ], "normalized": [] }, { "id": "2380", "type": "protein_molecule", "text": [ "AhR" ], "offsets": [ [ 970, 973 ] ], "normalized": [] }, { "id": "2381", "type": "other_name", "text": [ "BSAP-stimulated CD19 gene transcription" ], "offsets": [ [ 995, 1034 ] ], "normalized": [] }, { "id": "2382", "type": "protein_molecule", "text": [ "BSAP" ], "offsets": [ [ 995, 999 ] ], "normalized": [] }, { "id": "2383", "type": "DNA_domain_or_region", "text": [ "CD19 gene" ], "offsets": [ [ 1011, 1020 ] ], "normalized": [] }, { "id": "2384", "type": "DNA_domain_or_region", "text": [ "DNA binding site" ], "offsets": [ [ 1063, 1079 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "2386", "type": "title", "text": [ "Inhibitory action of nm23 proteins on induction of erythroid differentiation of human leukemia cells." ], "offsets": [ [ 0, 101 ] ] }, { "id": "2387", "type": "abstract", "text": [ "We recently identified a differentiation inhibitory factor (I-factor) in mouse myeloid leukemia M1 cells as a murine homolog of the human nm23-H2 gene product. nm23 genes encode proteins that participate in tumor metastasis regulation and in various fundamental cellular processes, although their mechanisms of action are still unknown. Although all nm23 proteins contain nucleoside diphosphate (NDP) kinase activity, it has not been established that the enzyme activity mediated the various functions of nm23 proteins. In the present experiment, we examined the effect of nm23 proteins on various differentiation induction systems of human leukemic cells including HL-60, U937, HEL/S, KU812F, K562, and HEL cells. Native human erythrocyte NDP kinase protein inhibited the induction of erythroid differentiation of HEL, KU812 and K562 cells, but not the induction of monocytic or granulocytic differentiation of HL-60, U937 and HEL/S cells. The erythroid differentiation of HEL cells was inhibited by recombinant human nm23-H1, -H2, mouse nm23-M1, and -M2 proteins. Moreover, both the mutant nm23-H2His protein and truncated nm23-H2 protein containing N-terminal (1-60) peptide, which do not have NDP kinase activity, also inhibited erythroid differentiation of HEL cells. These results suggest that (1) the differentiation inhibitory activity of I-factor/nm23 protein is not restricted to monocytic differentiation of M1 cells, (2) the inhibitory activity is exhibited without species specificity, and (3) the differentiation inhibitory activity of the nm23/NDP kinase protein is independent of its enzyme activity and requires the presence of N-terminal peptides." ], "offsets": [ [ 102, 1767 ] ] } ]

[ { "id": "2388", "type": "other_name", "text": [ "Inhibitory action" ], "offsets": [ [ 0, 17 ] ], "normalized": [] }, { "id": "2389", "type": "protein_family_or_group", "text": [ "nm23 proteins" ], "offsets": [ [ 21, 34 ] ], "normalized": [] }, { "id": "2390", "type": "other_name", "text": [ "erythroid differentiation" ], "offsets": [ [ 51, 76 ] ], "normalized": [] }, { "id": "2391", "type": "cell_type", "text": [ "human leukemia cells" ], "offsets": [ [ 80, 100 ] ], "normalized": [] }, { "id": "2392", "type": "protein_family_or_group", "text": [ "differentiation inhibitory factor" ], "offsets": [ [ 127, 160 ] ], "normalized": [] }, { "id": "2393", "type": "protein_family_or_group", "text": [ "I-factor" ], "offsets": [ [ 162, 170 ] ], "normalized": [] }, { "id": "2394", "type": "cell_line", "text": [ "mouse myeloid leukemia M1 cells" ], "offsets": [ [ 175, 206 ] ], "normalized": [] }, { "id": "2395", "type": "protein_family_or_group", "text": [ "murine homolog" ], "offsets": [ [ 212, 226 ] ], "normalized": [] }, { "id": "2396", "type": "protein_molecule", "text": [ "human nm23-H2 gene product" ], "offsets": [ [ 234, 260 ] ], "normalized": [] }, { "id": "2397", "type": "DNA_family_or_group", "text": [ "nm23 genes" ], "offsets": [ [ 262, 272 ] ], "normalized": [] }, { "id": "2398", "type": "other_name", "text": [ "tumor metastasis regulation" ], "offsets": [ [ 309, 336 ] ], "normalized": [] }, { "id": "2399", "type": "protein_family_or_group", "text": [ "nm23 proteins" ], "offsets": [ [ 452, 465 ] ], "normalized": [] }, { "id": "2400", "type": "other_name", "text": [ "nucleoside diphosphate (NDP) kinase activity" ], "offsets": [ [ 474, 518 ] ], "normalized": [] }, { "id": "2401", "type": "protein_family_or_group", "text": [ "nucleoside diphosphate (NDP) kinase" ], "offsets": [ [ 474, 509 ] ], "normalized": [] }, { "id": "2402", "type": "other_name", "text": [ "enzyme activity" ], "offsets": [ [ 557, 572 ] ], "normalized": [] }, { "id": "2403", "type": "protein_family_or_group", "text": [ "nm23 proteins" ], "offsets": [ [ 607, 620 ] ], "normalized": [] }, { "id": "2404", "type": "protein_family_or_group", "text": [ "nm23 proteins" ], "offsets": [ [ 675, 688 ] ], "normalized": [] }, { "id": "2405", "type": "cell_type", "text": [ "human leukemic cells" ], "offsets": [ [ 737, 757 ] ], "normalized": [] }, { "id": "2406", "type": "(AND cell_line cell_line cell_line cell_line cell_line cell_line)", "text": [ "HL-60, U937, HEL/S, KU812F, K562, and HEL cells" ], "offsets": [ [ 768, 815 ] ], "normalized": [] }, { "id": "2407", "type": "cell_line", "text": [ "HL-60" ], "offsets": [ [ 768, 773 ] ], "normalized": [] }, { "id": "2408", "type": "", "text": [ "HL-60" ], "offsets": [ [ 768, 773 ] ], "normalized": [] }, { "id": "2409", "type": "cell_line", "text": [ "U937" ], "offsets": [ [ 775, 779 ] ], "normalized": [] }, { "id": "2410", "type": "", "text": [ "U937" ], "offsets": [ [ 775, 779 ] ], "normalized": [] }, { "id": "2411", "type": "cell_line", "text": [ "HEL/S" ], "offsets": [ [ 781, 786 ] ], "normalized": [] }, { "id": "2412", "type": "", "text": [ "HEL/S" ], "offsets": [ [ 781, 786 ] ], "normalized": [] }, { "id": "2413", "type": "cell_line", "text": [ "KU812F" ], "offsets": [ [ 788, 794 ] ], "normalized": [] }, { "id": "2414", "type": "", "text": [ "KU812F" ], "offsets": [ [ 788, 794 ] ], "normalized": [] }, { "id": "2415", "type": "cell_line", "text": [ "K562" ], "offsets": [ [ 796, 800 ] ], "normalized": [] }, { "id": "2416", "type": "", "text": [ "K562" ], "offsets": [ [ 796, 800 ] ], "normalized": [] }, { "id": "2417", "type": "cell_line", "text": [ "HEL" ], "offsets": [ [ 781, 784 ] ], "normalized": [] }, { "id": "2418", "type": "", "text": [ "HEL" ], "offsets": [ [ 781, 784 ] ], "normalized": [] }, { "id": "2419", "type": "", "text": [ "cells" ], "offsets": [ [ 752, 757 ] ], "normalized": [] }, { "id": "2420", "type": "protein_family_or_group", "text": [ "Native human erythrocyte NDP kinase protein" ], "offsets": [ [ 817, 860 ] ], "normalized": [] }, { "id": "2421", "type": "other_name", "text": [ "erythroid differentiation" ], "offsets": [ [ 888, 913 ] ], "normalized": [] }, { "id": "2422", "type": "(AND cell_line cell_line cell_line)", "text": [ "HEL, KU812 and K562 cells" ], "offsets": [ [ 917, 942 ] ], "normalized": [] }, { "id": "2423", "type": "", "text": [ "HEL" ], "offsets": [ [ 917, 920 ] ], "normalized": [] }, { "id": "2424", "type": "", "text": [ "KU812" ], "offsets": [ [ 922, 927 ] ], "normalized": [] }, { "id": "2425", "type": "", "text": [ "K562" ], "offsets": [ [ 932, 936 ] ], "normalized": [] }, { "id": "2426", "type": "", "text": [ "cells" ], "offsets": [ [ 937, 942 ] ], "normalized": [] }, { "id": "2427", "type": "(OR other_name other_name)", "text": [ "monocytic or granulocytic differentiation" ], "offsets": [ [ 969, 1010 ] ], "normalized": [] }, { "id": "2428", "type": "", "text": [ "monocytic" ], "offsets": [ [ 969, 978 ] ], "normalized": [] }, { "id": "2429", "type": "", "text": [ "granulocytic" ], "offsets": [ [ 982, 994 ] ], "normalized": [] }, { "id": "2430", "type": "", "text": [ "differentiation" ], "offsets": [ [ 898, 913 ] ], "normalized": [] }, { "id": "2431", "type": "(AND cell_line cell_line cell_line)", "text": [ "HL-60, U937 and HEL/S cells" ], "offsets": [ [ 1014, 1041 ] ], "normalized": [] }, { "id": "2432", "type": "", "text": [ "HL-60" ], "offsets": [ [ 1014, 1019 ] ], "normalized": [] }, { "id": "2433", "type": "cell_line", "text": [ "HL-60" ], "offsets": [ [ 1014, 1019 ] ], "normalized": [] }, { "id": "2434", "type": "", "text": [ "U937" ], "offsets": [ [ 1021, 1025 ] ], "normalized": [] }, { "id": "2435", "type": "cell_line", "text": [ "U937" ], "offsets": [ [ 1021, 1025 ] ], "normalized": [] }, { "id": "2436", "type": "", "text": [ "HEL/S" ], "offsets": [ [ 1030, 1035 ] ], "normalized": [] }, { "id": "2437", "type": "cell_line", "text": [ "HEL/S" ], "offsets": [ [ 1030, 1035 ] ], "normalized": [] }, { "id": "2438", "type": "", "text": [ "cells" ], "offsets": [ [ 1036, 1041 ] ], "normalized": [] }, { "id": "2439", "type": "other_name", "text": [ "erythroid differentiation" ], "offsets": [ [ 1047, 1072 ] ], "normalized": [] }, { "id": "2440", "type": "cell_line", "text": [ "HEL cells" ], "offsets": [ [ 1076, 1085 ] ], "normalized": [] }, { "id": "2441", "type": "(AND protein_molecule protein_molecule protein_molecule protein_molecule)", "text": [ "recombinant human nm23-H1, -H2, mouse nm23-M1, and -M2 proteins" ], "offsets": [ [ 1103, 1166 ] ], "normalized": [] }, { "id": "2442", "type": "", "text": [ "recombinant" ], "offsets": [ [ 1103, 1114 ] ], "normalized": [] }, { "id": "2443", "type": "(AND protein_molecule protein_molecule)", "text": [ "human nm23-H1, -H2" ], "offsets": [ [ 1115, 1133 ] ], "normalized": [] }, { "id": "2444", "type": "", "text": [ "human nm23" ], "offsets": [ [ 1115, 1125 ] ], "normalized": [] }, { "id": "2445", "type": "multi_cell", "text": [ "human" ], "offsets": [ [ 1115, 1120 ] ], "normalized": [] }, { "id": "2446", "type": "", "text": [ "-H1" ], "offsets": [ [ 1125, 1128 ] ], "normalized": [] }, { "id": "2447", "type": "", "text": [ "-H2" ], "offsets": [ [ 1130, 1133 ] ], "normalized": [] }, { "id": "2448", "type": "(AND protein_molecule protein_molecule)", "text": [ "mouse nm23-M1, and -M2" ], "offsets": [ [ 1135, 1157 ] ], "normalized": [] }, { "id": "2449", "type": "", "text": [ "mouse nm23" ], "offsets": [ [ 1135, 1145 ] ], "normalized": [] }, { "id": "2450", "type": "multi_cell", "text": [ "mouse" ], "offsets": [ [ 1135, 1140 ] ], "normalized": [] }, { "id": "2451", "type": "", "text": [ "-M1" ], "offsets": [ [ 1145, 1148 ] ], "normalized": [] }, { "id": "2452", "type": "", "text": [ "-M2" ], "offsets": [ [ 1154, 1157 ] ], "normalized": [] }, { "id": "2453", "type": "", "text": [ "proteins" ], "offsets": [ [ 1158, 1166 ] ], "normalized": [] }, { "id": "2454", "type": "protein_molecule", "text": [ "mutant nm23-H2His protein" ], "offsets": [ [ 1187, 1212 ] ], "normalized": [] }, { "id": "2455", "type": "protein_molecule", "text": [ "truncated nm23-H2 protein" ], "offsets": [ [ 1217, 1242 ] ], "normalized": [] }, { "id": "2456", "type": "protein_domain_or_region", "text": [ "N-terminal (1-60) peptide" ], "offsets": [ [ 1254, 1279 ] ], "normalized": [] }, { "id": "2457", "type": "other_name", "text": [ "NDP kinase activity" ], "offsets": [ [ 1299, 1318 ] ], "normalized": [] }, { "id": "2458", "type": "protein_molecule", "text": [ "NDP kinase" ], "offsets": [ [ 1299, 1309 ] ], "normalized": [] }, { "id": "2459", "type": "other_name", "text": [ "erythroid differentiation" ], "offsets": [ [ 1335, 1360 ] ], "normalized": [] }, { "id": "2460", "type": "cell_line", "text": [ "HEL cells" ], "offsets": [ [ 1364, 1373 ] ], "normalized": [] }, { "id": "2461", "type": "other_name", "text": [ "differentiation inhibitory activity" ], "offsets": [ [ 1410, 1445 ] ], "normalized": [] }, { "id": "2462", "type": "protein_molecule", "text": [ "I-factor/nm23 protein" ], "offsets": [ [ 1449, 1470 ] ], "normalized": [] }, { "id": "2463", "type": "protein_family_or_group", "text": [ "I-factor" ], "offsets": [ [ 1449, 1457 ] ], "normalized": [] }, { "id": "2464", "type": "other_name", "text": [ "monocytic differentiation" ], "offsets": [ [ 1492, 1517 ] ], "normalized": [] }, { "id": "2465", "type": "cell_line", "text": [ "M1 cells" ], "offsets": [ [ 1521, 1529 ] ], "normalized": [] }, { "id": "2466", "type": "other_name", "text": [ "inhibitory activity" ], "offsets": [ [ 1426, 1445 ] ], "normalized": [] }, { "id": "2467", "type": "other_name", "text": [ "inhibitory activity" ], "offsets": [ [ 1539, 1558 ] ], "normalized": [] }, { "id": "2468", "type": "protein_molecule", "text": [ "nm23/NDP kinase protein" ], "offsets": [ [ 1656, 1679 ] ], "normalized": [] }, { "id": "2469", "type": "other_name", "text": [ "enzyme activity" ], "offsets": [ [ 1702, 1717 ] ], "normalized": [] }, { "id": "2470", "type": "peptide", "text": [ "N-terminal peptides" ], "offsets": [ [ 1747, 1766 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "2472", "type": "title", "text": [ "Lipopolysaccharide-induced E-selectin expression requires continuous presence of LPS and is inhibited by bactericidal/permeability-increasing protein." ], "offsets": [ [ 0, 150 ] ] }, { "id": "2473", "type": "abstract", "text": [ "Endothelial cells stimulated by LPS express E-selectin, which plays an important role in mediating neutrophil adhesion during inflammation. E-selectin is induced within 1-2 h, peaks at 4-6 h, and gradually returns to basal level by 24 h. rBPI21, a recombinant N-terminal fragment of human bactericidal/permeability-increasing protein (BPI), inhibited LPS-induced E-selectin expression when added at the same time as, and up to 6 h after, LPS. Delayed administration of rBPI21 also affected LPS-mediated activation of the nuclear factor, NF-kappa B. Two to 4 h following LPS addition to endothelial cells, when NF-kappa B was already activated, addition of rBPI21 resulted in marked reduction of NF-kappa B detectable at 4 or 6 h. These results indicate that endothelial activation requires continuous presence of LPS, and rBPI21 acts to reverse LPS-mediated endothelial activation by interrupting the on-going LPS signal." ], "offsets": [ [ 151, 1072 ] ] } ]

[ { "id": "2474", "type": "other_name", "text": [ "Lipopolysaccharide-induced E-selectin expression" ], "offsets": [ [ 0, 48 ] ], "normalized": [] }, { "id": "2475", "type": "lipid", "text": [ "Lipopolysaccharide" ], "offsets": [ [ 0, 18 ] ], "normalized": [] }, { "id": "2476", "type": "protein_molecule", "text": [ "E-selectin" ], "offsets": [ [ 27, 37 ] ], "normalized": [] }, { "id": "2477", "type": "lipid", "text": [ "LPS" ], "offsets": [ [ 81, 84 ] ], "normalized": [] }, { "id": "2478", "type": "protein_family_or_group", "text": [ "bactericidal/permeability-increasing protein" ], "offsets": [ [ 105, 149 ] ], "normalized": [] }, { "id": "2479", "type": "cell_type", "text": [ "Endothelial cells" ], "offsets": [ [ 151, 168 ] ], "normalized": [] }, { "id": "2480", "type": "lipid", "text": [ "LPS" ], "offsets": [ [ 183, 186 ] ], "normalized": [] }, { "id": "2481", "type": "protein_molecule", "text": [ "E-selectin" ], "offsets": [ [ 195, 205 ] ], "normalized": [] }, { "id": "2482", "type": "other_name", "text": [ "neutrophil adhesion" ], "offsets": [ [ 250, 269 ] ], "normalized": [] }, { "id": "2483", "type": "cell_type", "text": [ "neutrophil" ], "offsets": [ [ 250, 260 ] ], "normalized": [] }, { "id": "2484", "type": "other_name", "text": [ "inflammation" ], "offsets": [ [ 277, 289 ] ], "normalized": [] }, { "id": "2485", "type": "protein_molecule", "text": [ "E-selectin" ], "offsets": [ [ 291, 301 ] ], "normalized": [] }, { "id": "2486", "type": "protein_molecule", "text": [ "rBPI21" ], "offsets": [ [ 389, 395 ] ], "normalized": [] }, { "id": "2487", "type": "protein_family_or_group", "text": [ "recombinant N-terminal fragment" ], "offsets": [ [ 399, 430 ] ], "normalized": [] }, { "id": "2488", "type": "protein_molecule", "text": [ "human bactericidal/permeability-increasing protein" ], "offsets": [ [ 434, 484 ] ], "normalized": [] }, { "id": "2489", "type": "protein_molecule", "text": [ "BPI" ], "offsets": [ [ 390, 393 ] ], "normalized": [] }, { "id": "2490", "type": "other_name", "text": [ "LPS-induced E-selectin expression" ], "offsets": [ [ 502, 535 ] ], "normalized": [] }, { "id": "2491", "type": "lipid", "text": [ "LPS" ], "offsets": [ [ 502, 505 ] ], "normalized": [] }, { "id": "2492", "type": "protein_molecule", "text": [ "E-selectin" ], "offsets": [ [ 514, 524 ] ], "normalized": [] }, { "id": "2493", "type": "lipid", "text": [ "LPS" ], "offsets": [ [ 589, 592 ] ], "normalized": [] }, { "id": "2494", "type": "protein_molecule", "text": [ "rBPI21" ], "offsets": [ [ 620, 626 ] ], "normalized": [] }, { "id": "2495", "type": "other_name", "text": [ "LPS-mediated activation" ], "offsets": [ [ 641, 664 ] ], "normalized": [] }, { "id": "2496", "type": "lipid", "text": [ "LPS" ], "offsets": [ [ 641, 644 ] ], "normalized": [] }, { "id": "2497", "type": "protein_family_or_group", "text": [ "nuclear factor" ], "offsets": [ [ 672, 686 ] ], "normalized": [] }, { "id": "2498", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 688, 698 ] ], "normalized": [] }, { "id": "2499", "type": "lipid", "text": [ "LPS" ], "offsets": [ [ 721, 724 ] ], "normalized": [] }, { "id": "2500", "type": "cell_type", "text": [ "endothelial cells" ], "offsets": [ [ 737, 754 ] ], "normalized": [] }, { "id": "2501", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 761, 771 ] ], "normalized": [] }, { "id": "2502", "type": "protein_molecule", "text": [ "rBPI21" ], "offsets": [ [ 807, 813 ] ], "normalized": [] }, { "id": "2503", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 846, 856 ] ], "normalized": [] }, { "id": "2504", "type": "other_name", "text": [ "endothelial activation" ], "offsets": [ [ 909, 931 ] ], "normalized": [] }, { "id": "2505", "type": "lipid", "text": [ "LPS" ], "offsets": [ [ 964, 967 ] ], "normalized": [] }, { "id": "2506", "type": "protein_molecule", "text": [ "rBPI21" ], "offsets": [ [ 973, 979 ] ], "normalized": [] }, { "id": "2507", "type": "other_name", "text": [ "LPS-mediated endothelial activation" ], "offsets": [ [ 996, 1031 ] ], "normalized": [] }, { "id": "2508", "type": "lipid", "text": [ "LPS" ], "offsets": [ [ 996, 999 ] ], "normalized": [] }, { "id": "2509", "type": "other_name", "text": [ "on-going LPS signal" ], "offsets": [ [ 1052, 1071 ] ], "normalized": [] }, { "id": "2510", "type": "lipid", "text": [ "LPS" ], "offsets": [ [ 1061, 1064 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "2512", "type": "title", "text": [ "GM-CSF and IL-2 share common control mechanisms in response to costimulatory signals in T cells." ], "offsets": [ [ 0, 96 ] ] }, { "id": "2513", "type": "abstract", "text": [ "Antigen complexed with major histocompatibility complex class I or II molecules on the surface of antigen presenting cells interacts with the T cell receptor (TCR) on the surface of T cells and initiates an activation cascade. So called costimulatory signals, mediated by other cell surface interactions or soluble cytokines produced by antigen presenting cells, are also required for complete T cell activation. High levels of cytokine gene expression in T cells also required both TCR and costimulatory signals. The granulocyte-macrophage colony-stimulating factor requires sequences in the promoter as well as a powerful enhancer located 3kb upstream to respond to TCR-like signals. These promoter and enhancer regions are mainly activated by the transcription factor nuclear factor of activated T cells (NFAT). The activation of NFAT by TCR signals has been well described for interleukin-2 (IL-2) and IL-4 gene transcription in T cells. Costimulatory signals, such as activation of the CD28 cell surface molecule on T cells, lead to activation through a distinct region of the granulocyte-macrophage colony-stimulating factor (GM-CSF) promoter. This region is termed the CK-1 or CD28RE and appears to bind specific members of the NF-kappa B family of transcription factors. Human T leukemia virus type 1 (HTLV-1) infects T cells and can lead to increase GM-CSF expression. We have found that the HTLV-1 transactivator protein, tax, acts as a costimulatory signal for GM-CSF and IL-2 gene transcription, in that it can cooperate with TCR signals to mediate high level gene expression. Tax activates the GM-CSF promoter through the CK-1/CD28RE region and also activates nuclear factor-kappa B binding to this region. However, other transcription factors or coactivators of NF-kappa B are required for tax activation but these remain to be identified. The CK-1/CD28RE of GM-CSF shows a high degree of similarity to the IL-2 CD28RE and the IL-3 gene also contains a related region. This observation, together with the fact that both GM-CSF and IL-2 respond to TCR signals via NFAT, implies a high degree of conservation in the regulation of cytokine gene expression in T cells." ], "offsets": [ [ 97, 2275 ] ] } ]

[ { "id": "2514", "type": "protein_molecule", "text": [ "GM-CSF" ], "offsets": [ [ 0, 6 ] ], "normalized": [] }, { "id": "2515", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 11, 15 ] ], "normalized": [] }, { "id": "2516", "type": "other_name", "text": [ "control mechanisms" ], "offsets": [ [ 29, 47 ] ], "normalized": [] }, { "id": "2517", "type": "other_name", "text": [ "costimulatory signals" ], "offsets": [ [ 63, 84 ] ], "normalized": [] }, { "id": "2518", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 88, 95 ] ], "normalized": [] }, { "id": "2519", "type": "(OR protein_family_or_group protein_family_or_group)", "text": [ "major histocompatibility complex class I or II molecules" ], "offsets": [ [ 120, 176 ] ], "normalized": [] }, { "id": "2520", "type": "", "text": [ "major histocompatibility complex class" ], "offsets": [ [ 120, 158 ] ], "normalized": [] }, { "id": "2521", "type": "", "text": [ "I" ], "offsets": [ [ 159, 160 ] ], "normalized": [] }, { "id": "2522", "type": "", "text": [ "II" ], "offsets": [ [ 164, 166 ] ], "normalized": [] }, { "id": "2523", "type": "", "text": [ "molecules" ], "offsets": [ [ 167, 176 ] ], "normalized": [] }, { "id": "2524", "type": "cell_type", "text": [ "antigen presenting cells" ], "offsets": [ [ 195, 219 ] ], "normalized": [] }, { "id": "2525", "type": "protein_family_or_group", "text": [ "T cell receptor" ], "offsets": [ [ 239, 254 ] ], "normalized": [] }, { "id": "2526", "type": "protein_family_or_group", "text": [ "TCR" ], "offsets": [ [ 256, 259 ] ], "normalized": [] }, { "id": "2527", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 279, 286 ] ], "normalized": [] }, { "id": "2528", "type": "other_name", "text": [ "costimulatory signals" ], "offsets": [ [ 334, 355 ] ], "normalized": [] }, { "id": "2529", "type": "protein_family_or_group", "text": [ "soluble cytokines" ], "offsets": [ [ 404, 421 ] ], "normalized": [] }, { "id": "2530", "type": "cell_type", "text": [ "antigen presenting cells" ], "offsets": [ [ 434, 458 ] ], "normalized": [] }, { "id": "2531", "type": "other_name", "text": [ "T cell activation" ], "offsets": [ [ 491, 508 ] ], "normalized": [] }, { "id": "2532", "type": "other_name", "text": [ "cytokine gene expression" ], "offsets": [ [ 525, 549 ] ], "normalized": [] }, { "id": "2533", "type": "protein_family_or_group", "text": [ "cytokine" ], "offsets": [ [ 525, 533 ] ], "normalized": [] }, { "id": "2534", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 553, 560 ] ], "normalized": [] }, { "id": "2535", "type": "protein_family_or_group", "text": [ "TCR" ], "offsets": [ [ 580, 583 ] ], "normalized": [] }, { "id": "2536", "type": "other_name", "text": [ "costimulatory signals" ], "offsets": [ [ 588, 609 ] ], "normalized": [] }, { "id": "2537", "type": "protein_molecule", "text": [ "granulocyte-macrophage colony-stimulating factor" ], "offsets": [ [ 615, 663 ] ], "normalized": [] }, { "id": "2538", "type": "DNA_domain_or_region", "text": [ "promoter" ], "offsets": [ [ 690, 698 ] ], "normalized": [] }, { "id": "2539", "type": "DNA_domain_or_region", "text": [ "enhancer" ], "offsets": [ [ 721, 729 ] ], "normalized": [] }, { "id": "2540", "type": "other_name", "text": [ "TCR-like signals" ], "offsets": [ [ 765, 781 ] ], "normalized": [] }, { "id": "2541", "type": "protein_family_or_group", "text": [ "TCR" ], "offsets": [ [ 765, 768 ] ], "normalized": [] }, { "id": "2542", "type": "DNA_domain_or_region", "text": [ "promoter and enhancer regions" ], "offsets": [ [ 789, 818 ] ], "normalized": [] }, { "id": "2543", "type": "protein_family_or_group", "text": [ "transcription factor nuclear factor of activated T cells" ], "offsets": [ [ 847, 903 ] ], "normalized": [] }, { "id": "2544", "type": "protein_family_or_group", "text": [ "transcription factor" ], "offsets": [ [ 847, 867 ] ], "normalized": [] }, { "id": "2545", "type": "protein_family_or_group", "text": [ "nuclear factor" ], "offsets": [ [ 868, 882 ] ], "normalized": [] }, { "id": "2546", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 896, 903 ] ], "normalized": [] }, { "id": "2547", "type": "protein_family_or_group", "text": [ "NFAT" ], "offsets": [ [ 905, 909 ] ], "normalized": [] }, { "id": "2548", "type": "protein_family_or_group", "text": [ "NFAT" ], "offsets": [ [ 930, 934 ] ], "normalized": [] }, { "id": "2549", "type": "protein_family_or_group", "text": [ "TCR" ], "offsets": [ [ 938, 941 ] ], "normalized": [] }, { "id": "2550", "type": "(AND other_name other_name)", "text": [ "interleukin-2 (IL-2) and IL-4 gene transcription" ], "offsets": [ [ 978, 1026 ] ], "normalized": [] }, { "id": "2551", "type": "", "text": [ "interleukin-2 (IL-2)" ], "offsets": [ [ 978, 998 ] ], "normalized": [] }, { "id": "2552", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 993, 997 ] ], "normalized": [] }, { "id": "2553", "type": "", "text": [ "IL-4" ], "offsets": [ [ 1003, 1007 ] ], "normalized": [] }, { "id": "2554", "type": "", "text": [ "gene transcription" ], "offsets": [ [ 1008, 1026 ] ], "normalized": [] }, { "id": "2555", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 1030, 1037 ] ], "normalized": [] }, { "id": "2556", "type": "protein_molecule", "text": [ "CD28 cell surface molecule" ], "offsets": [ [ 1088, 1114 ] ], "normalized": [] }, { "id": "2557", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 1118, 1125 ] ], "normalized": [] }, { "id": "2558", "type": "DNA_domain_or_region", "text": [ "granulocyte-macrophage colony-stimulating factor (GM-CSF) promoter" ], "offsets": [ [ 1179, 1245 ] ], "normalized": [] }, { "id": "2559", "type": "protein_molecule", "text": [ "granulocyte-macrophage colony-stimulating factor" ], "offsets": [ [ 1179, 1227 ] ], "normalized": [] }, { "id": "2560", "type": "protein_molecule", "text": [ "GM-CSF" ], "offsets": [ [ 1229, 1235 ] ], "normalized": [] }, { "id": "2561", "type": "DNA_domain_or_region", "text": [ "CK-1" ], "offsets": [ [ 1273, 1277 ] ], "normalized": [] }, { "id": "2562", "type": "DNA_domain_or_region", "text": [ "CD28RE" ], "offsets": [ [ 1281, 1287 ] ], "normalized": [] }, { "id": "2563", "type": "protein_family_or_group", "text": [ "NF-kappa B family" ], "offsets": [ [ 1332, 1349 ] ], "normalized": [] }, { "id": "2564", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 1332, 1342 ] ], "normalized": [] }, { "id": "2565", "type": "protein_family_or_group", "text": [ "transcription factors" ], "offsets": [ [ 1353, 1374 ] ], "normalized": [] }, { "id": "2566", "type": "virus", "text": [ "Human T leukemia virus type 1" ], "offsets": [ [ 1376, 1405 ] ], "normalized": [] }, { "id": "2567", "type": "virus", "text": [ "HTLV-1" ], "offsets": [ [ 1407, 1413 ] ], "normalized": [] }, { "id": "2568", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 1423, 1430 ] ], "normalized": [] }, { "id": "2569", "type": "other_name", "text": [ "GM-CSF expression" ], "offsets": [ [ 1456, 1473 ] ], "normalized": [] }, { "id": "2570", "type": "protein_molecule", "text": [ "GM-CSF" ], "offsets": [ [ 1456, 1462 ] ], "normalized": [] }, { "id": "2571", "type": "protein_family_or_group", "text": [ "HTLV-1 transactivator protein" ], "offsets": [ [ 1498, 1527 ] ], "normalized": [] }, { "id": "2572", "type": "virus", "text": [ "HTLV-1" ], "offsets": [ [ 1498, 1504 ] ], "normalized": [] }, { "id": "2573", "type": "protein_molecule", "text": [ "tax" ], "offsets": [ [ 1529, 1532 ] ], "normalized": [] }, { "id": "2574", "type": "(AND other_name other_name)", "text": [ "GM-CSF and IL-2 gene transcription" ], "offsets": [ [ 1569, 1603 ] ], "normalized": [] }, { "id": "2575", "type": "", "text": [ "GM-CSF" ], "offsets": [ [ 1569, 1575 ] ], "normalized": [] }, { "id": "2576", "type": "", "text": [ "IL-2" ], "offsets": [ [ 1580, 1584 ] ], "normalized": [] }, { "id": "2577", "type": "", "text": [ "gene transcription" ], "offsets": [ [ 1585, 1603 ] ], "normalized": [] }, { "id": "2578", "type": "protein_family_or_group", "text": [ "TCR" ], "offsets": [ [ 1635, 1638 ] ], "normalized": [] }, { "id": "2579", "type": "other_name", "text": [ "gene expression" ], "offsets": [ [ 1669, 1684 ] ], "normalized": [] }, { "id": "2580", "type": "DNA_domain_or_region", "text": [ "GM-CSF promoter" ], "offsets": [ [ 1704, 1719 ] ], "normalized": [] }, { "id": "2581", "type": "protein_molecule", "text": [ "GM-CSF" ], "offsets": [ [ 1704, 1710 ] ], "normalized": [] }, { "id": "2582", "type": "DNA_domain_or_region", "text": [ "CK-1" ], "offsets": [ [ 1732, 1736 ] ], "normalized": [] }, { "id": "2583", "type": "DNA_domain_or_region", "text": [ "/CD28RE" ], "offsets": [ [ 1736, 1743 ] ], "normalized": [] }, { "id": "2584", "type": "other_name", "text": [ "nuclear factor-kappa B binding" ], "offsets": [ [ 1770, 1800 ] ], "normalized": [] }, { "id": "2585", "type": "protein_molecule", "text": [ "nuclear factor-kappa B" ], "offsets": [ [ 1770, 1792 ] ], "normalized": [] }, { "id": "2586", "type": "protein_family_or_group", "text": [ "transcription factors" ], "offsets": [ [ 1832, 1853 ] ], "normalized": [] }, { "id": "2587", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 1873, 1883 ] ], "normalized": [] }, { "id": "2588", "type": "other_name", "text": [ "tax activation" ], "offsets": [ [ 1901, 1915 ] ], "normalized": [] }, { "id": "2589", "type": "protein_molecule", "text": [ "tax" ], "offsets": [ [ 1901, 1904 ] ], "normalized": [] }, { "id": "2590", "type": "DNA_domain_or_region", "text": [ "CK-1" ], "offsets": [ [ 1955, 1959 ] ], "normalized": [] }, { "id": "2591", "type": "DNA_domain_or_region", "text": [ "/CD28RE" ], "offsets": [ [ 1959, 1966 ] ], "normalized": [] }, { "id": "2592", "type": "protein_molecule", "text": [ "GM-CSF" ], "offsets": [ [ 1970, 1976 ] ], "normalized": [] }, { "id": "2593", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 2018, 2022 ] ], "normalized": [] }, { "id": "2594", "type": "DNA_domain_or_region", "text": [ "CD28RE" ], "offsets": [ [ 1960, 1966 ] ], "normalized": [] }, { "id": "2595", "type": "DNA_domain_or_region", "text": [ "IL-3 gene" ], "offsets": [ [ 2038, 2047 ] ], "normalized": [] }, { "id": "2596", "type": "protein_molecule", "text": [ "GM-CSF" ], "offsets": [ [ 2131, 2137 ] ], "normalized": [] }, { "id": "2597", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 2142, 2146 ] ], "normalized": [] }, { "id": "2598", "type": "protein_family_or_group", "text": [ "TCR" ], "offsets": [ [ 2158, 2161 ] ], "normalized": [] }, { "id": "2599", "type": "protein_family_or_group", "text": [ "NFAT" ], "offsets": [ [ 2174, 2178 ] ], "normalized": [] }, { "id": "2600", "type": "other_name", "text": [ "cytokine gene expression" ], "offsets": [ [ 2239, 2263 ] ], "normalized": [] }, { "id": "2601", "type": "protein_family_or_group", "text": [ "cytokine" ], "offsets": [ [ 2239, 2247 ] ], "normalized": [] }, { "id": "2602", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 2267, 2274 ] ], "normalized": [] } ]

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[ { "id": "2604", "type": "title", "text": [ "Danazol decreases transcription of estrogen receptor gene in human monocytes." ], "offsets": [ [ 0, 77 ] ] }, { "id": "2605", "type": "abstract", "text": [ "1. Administration of danazol for over one month reduced the levels of estrogen receptor (ER) and its mRNA to approximately 50 and 20%, respectively in monocytes. 2. Danazol did not alter the degradation rate of ER mRNA in monocytes. 3. Danazol decreased the transcription rate of ER gene to approximately 50% in monocytes in a run-on assay. 4. Danazol may release estrogen predominance via the reduction of transcription for ER gene, which leads to the reduction of ER mRNA and ER expressions in monocytes." ], "offsets": [ [ 78, 584 ] ] } ]

[ { "id": "2606", "type": "other_organic_compound", "text": [ "Danazol" ], "offsets": [ [ 0, 7 ] ], "normalized": [] }, { "id": "2607", "type": "DNA_domain_or_region", "text": [ "estrogen receptor gene" ], "offsets": [ [ 35, 57 ] ], "normalized": [] }, { "id": "2608", "type": "protein_family_or_group", "text": [ "estrogen receptor" ], "offsets": [ [ 35, 52 ] ], "normalized": [] }, { "id": "2609", "type": "cell_type", "text": [ "human monocytes" ], "offsets": [ [ 61, 76 ] ], "normalized": [] }, { "id": "2610", "type": "other_organic_compound", "text": [ "danazol" ], "offsets": [ [ 99, 106 ] ], "normalized": [] }, { "id": "2611", "type": "protein_family_or_group", "text": [ "estrogen receptor" ], "offsets": [ [ 148, 165 ] ], "normalized": [] }, { "id": "2612", "type": "protein_family_or_group", "text": [ "ER" ], "offsets": [ [ 167, 169 ] ], "normalized": [] }, { "id": "2613", "type": "RNA_family_or_group", "text": [ "mRNA" ], "offsets": [ [ 179, 183 ] ], "normalized": [] }, { "id": "2614", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 229, 238 ] ], "normalized": [] }, { "id": "2615", "type": "other_organic_compound", "text": [ "Danazol" ], "offsets": [ [ 243, 250 ] ], "normalized": [] }, { "id": "2616", "type": "RNA_family_or_group", "text": [ "ER mRNA" ], "offsets": [ [ 289, 296 ] ], "normalized": [] }, { "id": "2617", "type": "protein_family_or_group", "text": [ "ER" ], "offsets": [ [ 289, 291 ] ], "normalized": [] }, { "id": "2618", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 300, 309 ] ], "normalized": [] }, { "id": "2619", "type": "other_organic_compound", "text": [ "Danazol" ], "offsets": [ [ 314, 321 ] ], "normalized": [] }, { "id": "2620", "type": "other_name", "text": [ "transcription rate" ], "offsets": [ [ 336, 354 ] ], "normalized": [] }, { "id": "2621", "type": "DNA_domain_or_region", "text": [ "ER gene" ], "offsets": [ [ 358, 365 ] ], "normalized": [] }, { "id": "2622", "type": "protein_family_or_group", "text": [ "ER" ], "offsets": [ [ 358, 360 ] ], "normalized": [] }, { "id": "2623", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 390, 399 ] ], "normalized": [] }, { "id": "2624", "type": "other_name", "text": [ "run-on assay" ], "offsets": [ [ 405, 417 ] ], "normalized": [] }, { "id": "2625", "type": "other_organic_compound", "text": [ "Danazol" ], "offsets": [ [ 422, 429 ] ], "normalized": [] }, { "id": "2626", "type": "lipid", "text": [ "estrogen" ], "offsets": [ [ 442, 450 ] ], "normalized": [] }, { "id": "2627", "type": "DNA_domain_or_region", "text": [ "ER gene" ], "offsets": [ [ 503, 510 ] ], "normalized": [] }, { "id": "2628", "type": "protein_family_or_group", "text": [ "ER" ], "offsets": [ [ 503, 505 ] ], "normalized": [] }, { "id": "2629", "type": "RNA_molecule", "text": [ "ER mRNA" ], "offsets": [ [ 544, 551 ] ], "normalized": [] }, { "id": "2630", "type": "protein_family_or_group", "text": [ "ER" ], "offsets": [ [ 544, 546 ] ], "normalized": [] }, { "id": "2631", "type": "other_name", "text": [ "ER expressions" ], "offsets": [ [ 556, 570 ] ], "normalized": [] }, { "id": "2632", "type": "protein_family_or_group", "text": [ "ER" ], "offsets": [ [ 556, 558 ] ], "normalized": [] }, { "id": "2633", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 574, 583 ] ], "normalized": [] } ]

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[ { "id": "2635", "type": "title", "text": [ "Functional characterization of novel IL-2 transcriptional inhibitors." ], "offsets": [ [ 0, 69 ] ] }, { "id": "2636", "type": "abstract", "text": [ "IL-2-mediated T cell proliferation is a critical early event in the inflammatory process. Formation of the NFAT-1 transcriptional complex on the IL-2 promoter is essential for IL-2 transcription. Using a cell line that is stably transfected with a trimer of the NFAT-1 regulatory element linked to a lac-Z reporter gene, we screened for inhibitors of NFAT-1-mediated beta-galactosidase activity. WIN 61058 and WIN 53071 were identified as microM inhibitors. These compounds also inhibited beta-galactosidase mRNA levels. Similar inhibition of NFAT-1-mediated gene expression was observed in a second cell line, which is stably transfected with NFAT-1 regulatory elements linked to the reporter gene for sCD8. At 10 microM, both compounds inhibited IL-2 mRNA and protein levels in the NFAT-1-linked lac-Z transfectants, and in human lymphocytes. Both compounds inhibited the mixed lymphocyte reaction, and this inhibition was reversed by exogenous IL-2. WIN 53071 inhibited IL-2 production induced in the calcium-dependent PMA and ionomycin pathway. Conversely, calcium-independent anti-CD28 Ab and PMA-induced IL-2 production was resistant. Both compounds altered the NFAT-1 transcriptional complex, causing its retarded mobility on gels. By these functional criteria, we believe we have identified two structurally distinct, novel inhibitors of NFAT-1-mediated transcription." ], "offsets": [ [ 70, 1446 ] ] } ]

[ { "id": "2637", "type": "other_name", "text": [ "IL-2 transcriptional inhibitors" ], "offsets": [ [ 37, 68 ] ], "normalized": [] }, { "id": "2638", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 37, 41 ] ], "normalized": [] }, { "id": "2639", "type": "other_name", "text": [ "IL-2-mediated T cell proliferation" ], "offsets": [ [ 70, 104 ] ], "normalized": [] }, { "id": "2640", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 70, 74 ] ], "normalized": [] }, { "id": "2641", "type": "cell_type", "text": [ "T cell" ], "offsets": [ [ 84, 90 ] ], "normalized": [] }, { "id": "2642", "type": "other_name", "text": [ "inflammatory process" ], "offsets": [ [ 138, 158 ] ], "normalized": [] }, { "id": "2643", "type": "protein_complex", "text": [ "NFAT-1 transcriptional complex" ], "offsets": [ [ 177, 207 ] ], "normalized": [] }, { "id": "2644", "type": "protein_family_or_group", "text": [ "NFAT" ], "offsets": [ [ 177, 181 ] ], "normalized": [] }, { "id": "2645", "type": "DNA_domain_or_region", "text": [ "IL-2 promoter" ], "offsets": [ [ 215, 228 ] ], "normalized": [] }, { "id": "2646", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 215, 219 ] ], "normalized": [] }, { "id": "2647", "type": "other_name", "text": [ "IL-2 transcription" ], "offsets": [ [ 246, 264 ] ], "normalized": [] }, { "id": "2648", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 246, 250 ] ], "normalized": [] }, { "id": "2649", "type": "DNA_domain_or_region", "text": [ "NFAT-1 regulatory element" ], "offsets": [ [ 332, 357 ] ], "normalized": [] }, { "id": "2650", "type": "protein_family_or_group", "text": [ "NFAT" ], "offsets": [ [ 332, 336 ] ], "normalized": [] }, { "id": "2651", "type": "DNA_domain_or_region", "text": [ "lac-Z reporter gene" ], "offsets": [ [ 370, 389 ] ], "normalized": [] }, { "id": "2652", "type": "other_name", "text": [ "NFAT-1-mediated beta-galactosidase activity" ], "offsets": [ [ 421, 464 ] ], "normalized": [] }, { "id": "2653", "type": "protein_family_or_group", "text": [ "NFAT" ], "offsets": [ [ 421, 425 ] ], "normalized": [] }, { "id": "2654", "type": "protein_molecule", "text": [ "beta-galactosidase" ], "offsets": [ [ 437, 455 ] ], "normalized": [] }, { "id": "2655", "type": "other_organic_compound", "text": [ "WIN 61058" ], "offsets": [ [ 466, 475 ] ], "normalized": [] }, { "id": "2656", "type": "other_organic_compound", "text": [ "WIN 53071" ], "offsets": [ [ 480, 489 ] ], "normalized": [] }, { "id": "2657", "type": "other_name", "text": [ "microM inhibitors" ], "offsets": [ [ 509, 526 ] ], "normalized": [] }, { "id": "2658", "type": "other_name", "text": [ "beta-galactosidase mRNA levels" ], "offsets": [ [ 559, 589 ] ], "normalized": [] }, { "id": "2659", "type": "RNA_molecule", "text": [ "beta-galactosidase mRNA" ], "offsets": [ [ 559, 582 ] ], "normalized": [] }, { "id": "2660", "type": "protein_molecule", "text": [ "beta-galactosidase" ], "offsets": [ [ 559, 577 ] ], "normalized": [] }, { "id": "2661", "type": "other_name", "text": [ "NFAT-1-mediated gene expression" ], "offsets": [ [ 613, 644 ] ], "normalized": [] }, { "id": "2662", "type": "protein_family_or_group", "text": [ "NFAT" ], "offsets": [ [ 613, 617 ] ], "normalized": [] }, { "id": "2663", "type": "cell_line", "text": [ "cell line" ], "offsets": [ [ 670, 679 ] ], "normalized": [] }, { "id": "2664", "type": "DNA_family_or_group", "text": [ "NFAT-1 regulatory elements" ], "offsets": [ [ 714, 740 ] ], "normalized": [] }, { "id": "2665", "type": "protein_family_or_group", "text": [ "NFAT" ], "offsets": [ [ 714, 718 ] ], "normalized": [] }, { "id": "2666", "type": "DNA_domain_or_region", "text": [ "reporter gene for sCD8" ], "offsets": [ [ 755, 777 ] ], "normalized": [] }, { "id": "2667", "type": "(AND other_name other_name)", "text": [ "IL-2 mRNA and protein levels" ], "offsets": [ [ 818, 846 ] ], "normalized": [] }, { "id": "2668", "type": "", "text": [ "IL-2" ], "offsets": [ [ 818, 822 ] ], "normalized": [] }, { "id": "2669", "type": "", "text": [ "mRNA" ], "offsets": [ [ 823, 827 ] ], "normalized": [] }, { "id": "2670", "type": "", "text": [ "protein" ], "offsets": [ [ 832, 839 ] ], "normalized": [] }, { "id": "2671", "type": "", "text": [ "levels" ], "offsets": [ [ 840, 846 ] ], "normalized": [] }, { "id": "2672", "type": "cell_line", "text": [ "NFAT-1-linked lac-Z transfectants" ], "offsets": [ [ 854, 887 ] ], "normalized": [] }, { "id": "2673", "type": "protein_family_or_group", "text": [ "NFAT" ], "offsets": [ [ 854, 858 ] ], "normalized": [] }, { "id": "2674", "type": "cell_type", "text": [ "human lymphocytes" ], "offsets": [ [ 896, 913 ] ], "normalized": [] }, { "id": "2675", "type": "other_name", "text": [ "mixed lymphocyte reaction" ], "offsets": [ [ 944, 969 ] ], "normalized": [] }, { "id": "2676", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 1017, 1021 ] ], "normalized": [] }, { "id": "2677", "type": "other_organic_compound", "text": [ "WIN 53071" ], "offsets": [ [ 1023, 1032 ] ], "normalized": [] }, { "id": "2678", "type": "other_name", "text": [ "IL-2 production" ], "offsets": [ [ 1043, 1058 ] ], "normalized": [] }, { "id": "2679", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 1043, 1047 ] ], "normalized": [] }, { "id": "2680", "type": "other_name", "text": [ "calcium-dependent PMA and ionomycin pathway" ], "offsets": [ [ 1074, 1117 ] ], "normalized": [] }, { "id": "2681", "type": "protein_molecule", "text": [ "calcium-independent anti-CD28 Ab" ], "offsets": [ [ 1131, 1163 ] ], "normalized": [] }, { "id": "2682", "type": "other_name", "text": [ "PMA-induced IL-2 production" ], "offsets": [ [ 1168, 1195 ] ], "normalized": [] }, { "id": "2683", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 1180, 1184 ] ], "normalized": [] }, { "id": "2684", "type": "protein_complex", "text": [ "NFAT-1 transcriptional complex" ], "offsets": [ [ 1238, 1268 ] ], "normalized": [] }, { "id": "2685", "type": "protein_family_or_group", "text": [ "NFAT" ], "offsets": [ [ 1238, 1242 ] ], "normalized": [] }, { "id": "2686", "type": "other_organic_compound", "text": [ "gels" ], "offsets": [ [ 1303, 1307 ] ], "normalized": [] }, { "id": "2687", "type": "other_name", "text": [ "novel inhibitors" ], "offsets": [ [ 1396, 1412 ] ], "normalized": [] }, { "id": "2688", "type": "other_name", "text": [ "NFAT-1-mediated transcription" ], "offsets": [ [ 1416, 1445 ] ], "normalized": [] }, { "id": "2689", "type": "protein_family_or_group", "text": [ "NFAT" ], "offsets": [ [ 1416, 1420 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "2691", "type": "title", "text": [ "Transcriptional regulation of the vacuolar H(+)-ATPase B2 subunit gene in differentiating THP-1 cells." ], "offsets": [ [ 0, 102 ] ] }, { "id": "2692", "type": "abstract", "text": [ "Monocyte-macrophage differentiation was used as a model system for studying gene regulation of the human vacuolar H(+)-ATPase (V-ATPase). We examined mRNA levels of various V-ATPase subunits during differentiation of both native monocytes and the cell line THP-1, and found that transcriptional and post-transcriptional mechanisms could account for increases in cell V-ATPase content. From nuclear runoff experiments, we found that one subunit in particular, the B2 isoform (Mr = 56,000), was amplified primarily by transcriptional means. We have begun to examine the structure of the B2 subunit promoter region. Isolation and sequencing of the first exon and 5'-flanking region of this gene reveal a TATA-less promoter with a high G + C content. Primer extension and ribonuclease protection analyses indicate a single major transcriptional start site. We transfected promoter-luciferase reporter plasmids into THP-1 cells to define sequences that mediate transcriptional control during monocyte differentiation. We found that sequences downstream from the transcriptional start site were sufficient to confer increased expression during THP-1 differentiation. DNase I footprinting and sequence analysis revealed the existence of multiple AP2 and Sp1 binding sites in the 5'-untranslated and proximal coding regions." ], "offsets": [ [ 103, 1419 ] ] } ]

[ { "id": "2693", "type": "other_name", "text": [ "Transcriptional regulation" ], "offsets": [ [ 0, 26 ] ], "normalized": [] }, { "id": "2694", "type": "DNA_domain_or_region", "text": [ "vacuolar H(+)-ATPase B2 subunit gene" ], "offsets": [ [ 34, 70 ] ], "normalized": [] }, { "id": "2695", "type": "protein_subunit", "text": [ "vacuolar H(+)-ATPase B2 subunit" ], "offsets": [ [ 34, 65 ] ], "normalized": [] }, { "id": "2696", "type": "cell_line", "text": [ "differentiating THP-1 cells" ], "offsets": [ [ 74, 101 ] ], "normalized": [] }, { "id": "2697", "type": "other_name", "text": [ "Monocyte-macrophage differentiation" ], "offsets": [ [ 103, 138 ] ], "normalized": [] }, { "id": "2698", "type": "other_name", "text": [ "gene regulation" ], "offsets": [ [ 179, 194 ] ], "normalized": [] }, { "id": "2699", "type": "protein_molecule", "text": [ "human vacuolar H(+)-ATPase" ], "offsets": [ [ 202, 228 ] ], "normalized": [] }, { "id": "2700", "type": "protein_molecule", "text": [ "V-ATPase" ], "offsets": [ [ 230, 238 ] ], "normalized": [] }, { "id": "2701", "type": "other_name", "text": [ "mRNA levels" ], "offsets": [ [ 253, 264 ] ], "normalized": [] }, { "id": "2702", "type": "RNA_family_or_group", "text": [ "mRNA" ], "offsets": [ [ 253, 257 ] ], "normalized": [] }, { "id": "2703", "type": "protein_molecule", "text": [ "V-ATPase" ], "offsets": [ [ 276, 284 ] ], "normalized": [] }, { "id": "2704", "type": "cell_type", "text": [ "native monocytes" ], "offsets": [ [ 325, 341 ] ], "normalized": [] }, { "id": "2705", "type": "cell_line", "text": [ "cell line" ], "offsets": [ [ 350, 359 ] ], "normalized": [] }, { "id": "2706", "type": "cell_line", "text": [ "THP-1" ], "offsets": [ [ 360, 365 ] ], "normalized": [] }, { "id": "2707", "type": "(AND other_name other_name)", "text": [ "transcriptional and post-transcriptional mechanisms" ], "offsets": [ [ 382, 433 ] ], "normalized": [] }, { "id": "2708", "type": "", "text": [ "transcriptional" ], "offsets": [ [ 382, 397 ] ], "normalized": [] }, { "id": "2709", "type": "", "text": [ "post-transcriptional" ], "offsets": [ [ 402, 422 ] ], "normalized": [] }, { "id": "2710", "type": "", "text": [ "mechanisms" ], "offsets": [ [ 423, 433 ] ], "normalized": [] }, { "id": "2711", "type": "other_name", "text": [ "cell V-ATPase content" ], "offsets": [ [ 465, 486 ] ], "normalized": [] }, { "id": "2712", "type": "protein_molecule", "text": [ "V-ATPase" ], "offsets": [ [ 470, 478 ] ], "normalized": [] }, { "id": "2713", "type": "protein_subunit", "text": [ "B2 isoform" ], "offsets": [ [ 566, 576 ] ], "normalized": [] }, { "id": "2714", "type": "other_name", "text": [ "transcriptional means" ], "offsets": [ [ 619, 640 ] ], "normalized": [] }, { "id": "2715", "type": "DNA_domain_or_region", "text": [ "B2 subunit promoter region" ], "offsets": [ [ 688, 714 ] ], "normalized": [] }, { "id": "2716", "type": "protein_subunit", "text": [ "B2 subunit" ], "offsets": [ [ 688, 698 ] ], "normalized": [] }, { "id": "2717", "type": "DNA_domain_or_region", "text": [ "promoter region" ], "offsets": [ [ 699, 714 ] ], "normalized": [] }, { "id": "2718", "type": "DNA_domain_or_region", "text": [ "first exon" ], "offsets": [ [ 748, 758 ] ], "normalized": [] }, { "id": "2719", "type": "DNA_domain_or_region", "text": [ "5'-flanking region" ], "offsets": [ [ 763, 781 ] ], "normalized": [] }, { "id": "2720", "type": "DNA_domain_or_region", "text": [ "TATA-less promoter" ], "offsets": [ [ 804, 822 ] ], "normalized": [] }, { "id": "2721", "type": "other_name", "text": [ "G + C content" ], "offsets": [ [ 835, 848 ] ], "normalized": [] }, { "id": "2722", "type": "nucleotide", "text": [ "G" ], "offsets": [ [ 835, 836 ] ], "normalized": [] }, { "id": "2723", "type": "nucleotide", "text": [ "C" ], "offsets": [ [ 839, 840 ] ], "normalized": [] }, { "id": "2724", "type": "other_name", "text": [ "Primer extension" ], "offsets": [ [ 850, 866 ] ], "normalized": [] }, { "id": "2725", "type": "other_name", "text": [ "ribonuclease protection analyses" ], "offsets": [ [ 871, 903 ] ], "normalized": [] }, { "id": "2726", "type": "protein_molecule", "text": [ "ribonuclease" ], "offsets": [ [ 871, 883 ] ], "normalized": [] }, { "id": "2727", "type": "DNA_domain_or_region", "text": [ "major transcriptional start site" ], "offsets": [ [ 922, 954 ] ], "normalized": [] }, { "id": "2728", "type": "DNA_molecule", "text": [ "promoter-luciferase reporter plasmids" ], "offsets": [ [ 971, 1008 ] ], "normalized": [] }, { "id": "2729", "type": "cell_line", "text": [ "THP-1 cells" ], "offsets": [ [ 1014, 1025 ] ], "normalized": [] }, { "id": "2730", "type": "other_name", "text": [ "transcriptional control" ], "offsets": [ [ 1059, 1082 ] ], "normalized": [] }, { "id": "2731", "type": "other_name", "text": [ "monocyte differentiation" ], "offsets": [ [ 1090, 1114 ] ], "normalized": [] }, { "id": "2732", "type": "other_name", "text": [ "THP-1 differentiation" ], "offsets": [ [ 1241, 1262 ] ], "normalized": [] }, { "id": "2733", "type": "cell_line", "text": [ "THP-1" ], "offsets": [ [ 1241, 1246 ] ], "normalized": [] }, { "id": "2734", "type": "other_name", "text": [ "DNase I footprinting" ], "offsets": [ [ 1264, 1284 ] ], "normalized": [] }, { "id": "2735", "type": "protein_molecule", "text": [ "DNase I" ], "offsets": [ [ 1264, 1271 ] ], "normalized": [] }, { "id": "2736", "type": "other_name", "text": [ "sequence analysis" ], "offsets": [ [ 1289, 1306 ] ], "normalized": [] }, { "id": "2737", "type": "(AND DNA_domain_or_region DNA_domain_or_region)", "text": [ "AP2 and Sp1 binding sites" ], "offsets": [ [ 1342, 1367 ] ], "normalized": [] }, { "id": "2738", "type": "", "text": [ "AP2" ], "offsets": [ [ 1342, 1345 ] ], "normalized": [] }, { "id": "2739", "type": "", "text": [ "Sp1" ], "offsets": [ [ 1350, 1353 ] ], "normalized": [] }, { "id": "2740", "type": "", "text": [ "binding sites" ], "offsets": [ [ 1354, 1367 ] ], "normalized": [] }, { "id": "2741", "type": "(AND DNA_domain_or_region DNA_domain_or_region)", "text": [ "5'-untranslated and proximal coding regions" ], "offsets": [ [ 1375, 1418 ] ], "normalized": [] }, { "id": "2742", "type": "", "text": [ "5'-untranslated" ], "offsets": [ [ 1375, 1390 ] ], "normalized": [] }, { "id": "2743", "type": "", "text": [ "proximal coding" ], "offsets": [ [ 1395, 1410 ] ], "normalized": [] }, { "id": "2744", "type": "", "text": [ "regions" ], "offsets": [ [ 1411, 1418 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "2746", "type": "title", "text": [ "Synergy between signal transduction pathways is obligatory for expression of c-fos in B and T cell lines: implication for c-fos control via surface immunoglobulin and T cell antigen receptors." ], "offsets": [ [ 0, 192 ] ] }, { "id": "2747", "type": "abstract", "text": [ "Expression of the protooncogene c-fos is controlled by three main regulatory pathways involving kinase C, cAMP, and calcium. Kinase C mediates its effects via phosphorylation of serum response factor (SRF) which interacts with the serum response element (SRE); cAMP and calcium mediate their effects via phosphorylation of CREB (cAMP regulatory element binding protein) presumably by activation of a protein kinase A or calmodulin-regulated kinase. We have examined the function of these elements in Burkitt's lymphoma cells (Ramos and Daudi) as well as a T lymphocytic cell line (Jurkat). We have found that stimulation of any one of these pathways alone has little or no effect on c-fos induction. However, kinase C activation (PMA stimulation) combined with either cAMP (forskolin plus MIX) or calcium stimulation (ionophore) leads to greatly enhanced c-fos induction. By contrast, cAMP in the presence of calcium shows no synergy in c-fos induction. Okadaic acid augments PMA- as well as calcium-mediated activation of c-fos, and has little or no effect when combined with cAMP. The main difference between Ramos (B cells) and Jurkat (T cells) in the regulation of c-fos is that cAMP plus calcium is strongly synergistic in Jurkat and is without effect in Ramos. Analysis of AP-1 activity using gel mobility shift assays confirms that the requirements for synergy in c-fos mRNA induction are paralleled by requirements for synergy in induction of AP-1 activity. Signaling in B cells due to anti-Ig stimulation involves both kinase C activation and release of intracellular calcium, and results in c-fos mRNA induction. Our results indicate that synergy between the kinase C activation and calcium is needed for efficient c-fos induction since neither of these two alone induces c-fos well. That synergy of signaling pathways is relevant for the anti-Ig induction of c-fos is supported by the fact that cAMP-inducing agents and okadaic acid further enhance anti-Ig induction of c-fos. These results suggest that cell-specific patterns of synergy are an essential feature for c-fos induction and may be relevant for c-fos control through B and T cell antigen receptors." ], "offsets": [ [ 193, 2364 ] ] } ]

[ { "id": "2748", "type": "other_name", "text": [ "signal transduction pathways" ], "offsets": [ [ 16, 44 ] ], "normalized": [] }, { "id": "2749", "type": "DNA_domain_or_region", "text": [ "c-fos" ], "offsets": [ [ 77, 82 ] ], "normalized": [] }, { "id": "2750", "type": "(AND cell_line cell_line)", "text": [ "B and T cell lines" ], "offsets": [ [ 86, 104 ] ], "normalized": [] }, { "id": "2751", "type": "", "text": [ "B" ], "offsets": [ [ 86, 87 ] ], "normalized": [] }, { "id": "2752", "type": "", "text": [ "T" ], "offsets": [ [ 92, 93 ] ], "normalized": [] }, { "id": "2753", "type": "", "text": [ "cell lines" ], "offsets": [ [ 94, 104 ] ], "normalized": [] }, { "id": "2754", "type": "DNA_domain_or_region", "text": [ "c-fos" ], "offsets": [ [ 122, 127 ] ], "normalized": [] }, { "id": "2755", "type": "protein_family_or_group", "text": [ "surface immunoglobulin" ], "offsets": [ [ 140, 162 ] ], "normalized": [] }, { "id": "2756", "type": "protein_family_or_group", "text": [ "T cell antigen receptors" ], "offsets": [ [ 167, 191 ] ], "normalized": [] }, { "id": "2757", "type": "DNA_family_or_group", "text": [ "protooncogene c-fos" ], "offsets": [ [ 211, 230 ] ], "normalized": [] }, { "id": "2758", "type": "DNA_domain_or_region", "text": [ "c-fos" ], "offsets": [ [ 225, 230 ] ], "normalized": [] }, { "id": "2759", "type": "other_name", "text": [ "regulatory pathways" ], "offsets": [ [ 259, 278 ] ], "normalized": [] }, { "id": "2760", "type": "protein_molecule", "text": [ "kinase C" ], "offsets": [ [ 289, 297 ] ], "normalized": [] }, { "id": "2761", "type": "nucleotide", "text": [ "cAMP" ], "offsets": [ [ 299, 303 ] ], "normalized": [] }, { "id": "2762", "type": "atom", "text": [ "calcium" ], "offsets": [ [ 309, 316 ] ], "normalized": [] }, { "id": "2763", "type": "protein_family_or_group", "text": [ "Kinase C" ], "offsets": [ [ 318, 326 ] ], "normalized": [] }, { "id": "2764", "type": "other_name", "text": [ "phosphorylation" ], "offsets": [ [ 352, 367 ] ], "normalized": [] }, { "id": "2765", "type": "protein_molecule", "text": [ "serum response factor" ], "offsets": [ [ 371, 392 ] ], "normalized": [] }, { "id": "2766", "type": "protein_molecule", "text": [ "SRF" ], "offsets": [ [ 394, 397 ] ], "normalized": [] }, { "id": "2767", "type": "DNA_domain_or_region", "text": [ "serum response element" ], "offsets": [ [ 424, 446 ] ], "normalized": [] }, { "id": "2768", "type": "DNA_domain_or_region", "text": [ "SRE" ], "offsets": [ [ 448, 451 ] ], "normalized": [] }, { "id": "2769", "type": "nucleotide", "text": [ "cAMP" ], "offsets": [ [ 454, 458 ] ], "normalized": [] }, { "id": "2770", "type": "atom", "text": [ "calcium" ], "offsets": [ [ 463, 470 ] ], "normalized": [] }, { "id": "2771", "type": "other_name", "text": [ "phosphorylation" ], "offsets": [ [ 497, 512 ] ], "normalized": [] }, { "id": "2772", "type": "protein_molecule", "text": [ "CREB" ], "offsets": [ [ 516, 520 ] ], "normalized": [] }, { "id": "2773", "type": "protein_molecule", "text": [ "cAMP regulatory element binding protein" ], "offsets": [ [ 522, 561 ] ], "normalized": [] }, { "id": "2774", "type": "nucleotide", "text": [ "cAMP" ], "offsets": [ [ 522, 526 ] ], "normalized": [] }, { "id": "2775", "type": "protein_molecule", "text": [ "protein kinase A" ], "offsets": [ [ 593, 609 ] ], "normalized": [] }, { "id": "2776", "type": "protein_family_or_group", "text": [ "calmodulin-regulated kinase" ], "offsets": [ [ 613, 640 ] ], "normalized": [] }, { "id": "2777", "type": "cell_line", "text": [ "Burkitt's lymphoma cells" ], "offsets": [ [ 693, 717 ] ], "normalized": [] }, { "id": "2778", "type": "cell_line", "text": [ "Ramos" ], "offsets": [ [ 719, 724 ] ], "normalized": [] }, { "id": "2779", "type": "cell_line", "text": [ "Daudi" ], "offsets": [ [ 729, 734 ] ], "normalized": [] }, { "id": "2780", "type": "cell_line", "text": [ "T lymphocytic cell line" ], "offsets": [ [ 749, 772 ] ], "normalized": [] }, { "id": "2781", "type": "cell_line", "text": [ "Jurkat" ], "offsets": [ [ 774, 780 ] ], "normalized": [] }, { "id": "2782", "type": "other_name", "text": [ "c-fos induction" ], "offsets": [ [ 876, 891 ] ], "normalized": [] }, { "id": "2783", "type": "DNA_domain_or_region", "text": [ "c-fos" ], "offsets": [ [ 876, 881 ] ], "normalized": [] }, { "id": "2784", "type": "other_name", "text": [ "kinase C activation" ], "offsets": [ [ 902, 921 ] ], "normalized": [] }, { "id": "2785", "type": "protein_molecule", "text": [ "kinase C" ], "offsets": [ [ 902, 910 ] ], "normalized": [] }, { "id": "2786", "type": "other_name", "text": [ "PMA stimulation" ], "offsets": [ [ 923, 938 ] ], "normalized": [] }, { "id": "2787", "type": "other_organic_compound", "text": [ "PMA" ], "offsets": [ [ 923, 926 ] ], "normalized": [] }, { "id": "2788", "type": "nucleotide", "text": [ "cAMP" ], "offsets": [ [ 961, 965 ] ], "normalized": [] }, { "id": "2789", "type": "other_organic_compound", "text": [ "forskolin plus MIX" ], "offsets": [ [ 967, 985 ] ], "normalized": [] }, { "id": "2790", "type": "other_name", "text": [ "calcium stimulation" ], "offsets": [ [ 990, 1009 ] ], "normalized": [] }, { "id": "2791", "type": "atom", "text": [ "calcium" ], "offsets": [ [ 990, 997 ] ], "normalized": [] }, { "id": "2792", "type": "other_name", "text": [ "ionophore" ], "offsets": [ [ 1011, 1020 ] ], "normalized": [] }, { "id": "2793", "type": "other_name", "text": [ "c-fos induction" ], "offsets": [ [ 1048, 1063 ] ], "normalized": [] }, { "id": "2794", "type": "DNA_domain_or_region", "text": [ "c-fos" ], "offsets": [ [ 1048, 1053 ] ], "normalized": [] }, { "id": "2795", "type": "nucleotide", "text": [ "cAMP" ], "offsets": [ [ 1078, 1082 ] ], "normalized": [] }, { "id": "2796", "type": "atom", "text": [ "calcium" ], "offsets": [ [ 1102, 1109 ] ], "normalized": [] }, { "id": "2797", "type": "other_name", "text": [ "c-fos induction" ], "offsets": [ [ 1130, 1145 ] ], "normalized": [] }, { "id": "2798", "type": "DNA_domain_or_region", "text": [ "c-fos" ], "offsets": [ [ 1130, 1135 ] ], "normalized": [] }, { "id": "2799", "type": "other_organic_compound", "text": [ "Okadaic acid" ], "offsets": [ [ 1147, 1159 ] ], "normalized": [] }, { "id": "2800", "type": "(AS_WELL_AS other_name other_name)", "text": [ "PMA- as well as calcium-mediated activation" ], "offsets": [ [ 1169, 1212 ] ], "normalized": [] }, { "id": "2801", "type": "", "text": [ "PMA-" ], "offsets": [ [ 1169, 1173 ] ], "normalized": [] }, { "id": "2802", "type": "", "text": [ "calcium-" ], "offsets": [ [ 1185, 1193 ] ], "normalized": [] }, { "id": "2803", "type": "", "text": [ "mediated activation" ], "offsets": [ [ 1193, 1212 ] ], "normalized": [] }, { "id": "2804", "type": "DNA_domain_or_region", "text": [ "c-fos" ], "offsets": [ [ 1216, 1221 ] ], "normalized": [] }, { "id": "2805", "type": "nucleotide", "text": [ "cAMP" ], "offsets": [ [ 1270, 1274 ] ], "normalized": [] }, { "id": "2806", "type": "cell_line", "text": [ "Ramos" ], "offsets": [ [ 1304, 1309 ] ], "normalized": [] }, { "id": "2807", "type": "cell_type", "text": [ "B cells" ], "offsets": [ [ 1311, 1318 ] ], "normalized": [] }, { "id": "2808", "type": "cell_line", "text": [ "Jurkat" ], "offsets": [ [ 1324, 1330 ] ], "normalized": [] }, { "id": "2809", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 1332, 1339 ] ], "normalized": [] }, { "id": "2810", "type": "DNA_domain_or_region", "text": [ "c-fos" ], "offsets": [ [ 1362, 1367 ] ], "normalized": [] }, { "id": "2811", "type": "nucleotide", "text": [ "cAMP" ], "offsets": [ [ 1376, 1380 ] ], "normalized": [] }, { "id": "2812", "type": "atom", "text": [ "calcium" ], "offsets": [ [ 1386, 1393 ] ], "normalized": [] }, { "id": "2813", "type": "cell_line", "text": [ "Jurkat" ], "offsets": [ [ 1421, 1427 ] ], "normalized": [] }, { "id": "2814", "type": "cell_line", "text": [ "Ramos" ], "offsets": [ [ 1453, 1458 ] ], "normalized": [] }, { "id": "2815", "type": "other_name", "text": [ "AP-1 activity" ], "offsets": [ [ 1472, 1485 ] ], "normalized": [] }, { "id": "2816", "type": "protein_molecule", "text": [ "AP-1" ], "offsets": [ [ 1472, 1476 ] ], "normalized": [] }, { "id": "2817", "type": "other_name", "text": [ "gel mobility shift assays" ], "offsets": [ [ 1492, 1517 ] ], "normalized": [] }, { "id": "2818", "type": "other_name", "text": [ "c-fos mRNA induction" ], "offsets": [ [ 1564, 1584 ] ], "normalized": [] }, { "id": "2819", "type": "RNA_molecule", "text": [ "c-fos mRNA" ], "offsets": [ [ 1564, 1574 ] ], "normalized": [] }, { "id": "2820", "type": "DNA_domain_or_region", "text": [ "c-fos" ], "offsets": [ [ 1564, 1569 ] ], "normalized": [] }, { "id": "2821", "type": "other_name", "text": [ "AP-1 activity" ], "offsets": [ [ 1644, 1657 ] ], "normalized": [] }, { "id": "2822", "type": "protein_molecule", "text": [ "AP-1" ], "offsets": [ [ 1644, 1648 ] ], "normalized": [] }, { "id": "2823", "type": "cell_type", "text": [ "B cells" ], "offsets": [ [ 1672, 1679 ] ], "normalized": [] }, { "id": "2824", "type": "other_name", "text": [ "anti-Ig stimulation" ], "offsets": [ [ 1687, 1706 ] ], "normalized": [] }, { "id": "2825", "type": "protein_family_or_group", "text": [ "anti-Ig" ], "offsets": [ [ 1687, 1694 ] ], "normalized": [] }, { "id": "2826", "type": "protein_molecule", "text": [ "kinase C" ], "offsets": [ [ 1721, 1729 ] ], "normalized": [] }, { "id": "2827", "type": "atom", "text": [ "calcium" ], "offsets": [ [ 1770, 1777 ] ], "normalized": [] }, { "id": "2828", "type": "other_name", "text": [ "c-fos mRNA induction" ], "offsets": [ [ 1794, 1814 ] ], "normalized": [] }, { "id": "2829", "type": "RNA_molecule", "text": [ "c-fos mRNA" ], "offsets": [ [ 1794, 1804 ] ], "normalized": [] }, { "id": "2830", "type": "DNA_domain_or_region", "text": [ "c-fos" ], "offsets": [ [ 1794, 1799 ] ], "normalized": [] }, { "id": "2831", "type": "other_name", "text": [ "kinase C activation" ], "offsets": [ [ 1862, 1881 ] ], "normalized": [] }, { "id": "2832", "type": "protein_molecule", "text": [ "kinase C" ], "offsets": [ [ 1862, 1870 ] ], "normalized": [] }, { "id": "2833", "type": "atom", "text": [ "calcium" ], "offsets": [ [ 1886, 1893 ] ], "normalized": [] }, { "id": "2834", "type": "other_name", "text": [ "c-fos induction" ], "offsets": [ [ 1918, 1933 ] ], "normalized": [] }, { "id": "2835", "type": "DNA_domain_or_region", "text": [ "c-fos" ], "offsets": [ [ 1918, 1923 ] ], "normalized": [] }, { "id": "2836", "type": "DNA_domain_or_region", "text": [ "c-fos" ], "offsets": [ [ 1975, 1980 ] ], "normalized": [] }, { "id": "2837", "type": "other_name", "text": [ "anti-Ig induction" ], "offsets": [ [ 2042, 2059 ] ], "normalized": [] }, { "id": "2838", "type": "protein_family_or_group", "text": [ "anti-Ig" ], "offsets": [ [ 2042, 2049 ] ], "normalized": [] }, { "id": "2839", "type": "DNA_domain_or_region", "text": [ "c-fos" ], "offsets": [ [ 2063, 2068 ] ], "normalized": [] }, { "id": "2840", "type": "other_name", "text": [ "cAMP-inducing agents" ], "offsets": [ [ 2099, 2119 ] ], "normalized": [] }, { "id": "2841", "type": "nucleotide", "text": [ "cAMP" ], "offsets": [ [ 2099, 2103 ] ], "normalized": [] }, { "id": "2842", "type": "other_name", "text": [ "anti-Ig induction" ], "offsets": [ [ 2153, 2170 ] ], "normalized": [] }, { "id": "2843", "type": "protein_family_or_group", "text": [ "anti-Ig" ], "offsets": [ [ 2153, 2160 ] ], "normalized": [] }, { "id": "2844", "type": "DNA_domain_or_region", "text": [ "c-fos" ], "offsets": [ [ 2174, 2179 ] ], "normalized": [] }, { "id": "2845", "type": "other_name", "text": [ "c-fos induction" ], "offsets": [ [ 2271, 2286 ] ], "normalized": [] }, { "id": "2846", "type": "DNA_domain_or_region", "text": [ "c-fos" ], "offsets": [ [ 2271, 2276 ] ], "normalized": [] }, { "id": "2847", "type": "other_name", "text": [ "c-fos control" ], "offsets": [ [ 2311, 2324 ] ], "normalized": [] }, { "id": "2848", "type": "DNA_domain_or_region", "text": [ "c-fos" ], "offsets": [ [ 2311, 2316 ] ], "normalized": [] }, { "id": "2849", "type": "(AND protein_family_or_group protein_family_or_group)", "text": [ "B and T cell antigen receptors" ], "offsets": [ [ 2333, 2363 ] ], "normalized": [] }, { "id": "2850", "type": "", "text": [ "B" ], "offsets": [ [ 2333, 2334 ] ], "normalized": [] }, { "id": "2851", "type": "", "text": [ "T" ], "offsets": [ [ 2181, 2182 ] ], "normalized": [] }, { "id": "2852", "type": "", "text": [ "cell antigen receptors" ], "offsets": [ [ 2341, 2363 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "2854", "type": "title", "text": [ "Multiple signals are required for function of the human granulocyte-macrophage colony-stimulating factor gene promoter in T cells." ], "offsets": [ [ 0, 130 ] ] }, { "id": "2855", "type": "abstract", "text": [ "The human granulocyte-macrophage CSF (GM-CSF) gene is expressed in T cells in response to TCR activation that can be mimicked by treatment of the cells with PMA and Ca2+ ionophore. The gene contains a proximal functional promoter region (-620 to +34), as well as a powerful enhancer located 3 kb upstream, both of which are involved in the response of the gene to TCR activation. The proximal promoter contains a region termed CLEO (-54 to -31) that consists of a purine-rich element abutting an activator protein-1 (AP-1)-like site, as well as an upstream nuclear factor-kappa B (NF-kappa B) site (-85 to -76) and a CK-1 element (-101 to -92). We show in this work that mutations in either the purine-rich region of the CLEO element or the NF-kappa B site result in reduced PMA/Ca2+ activation of a 620-bp human GM-CSF promoter-luciferase reporter construct in Jurkat T cells by 65% and 50%, respectively. The major inducible protein complex that binds to the human CLEO (hCLEO) element is an AP-1-like complex that is inducible by PMA alone, but shows increased binding in response to PMA together with Ca2+ ionophore. Although the binding of this complex is not cyclosporin-sensitive, promoter induction is inhibited by cyclosporin treatment. A second weak inducible complex resembling nuclear factor of activated T cells (NF-AT) was also observed binding to the hCLEO region. By using recombinant proteins, we confirmed that AP-1, NF-ATp, and a higher order NF-ATp/AP-1 complex could all form with the hCLEO element, and we have also defined the sequence requirements for binding of each of these complexes. We found that expression of a constitutively active form of calcineurin could substitute for Ca2+ ionophore and synergize with PMA to activate the GM-CSF promoter, and conversely that mutant-activated Ras could substitute for PMA and cooperate with Ca2+ ionophore. Co-expression of Ras and calcineurin, however, did not activate the GM-CSF promoter, but required the additional expression of NF-kappa B p65. These results imply that at least three signals are required to activate the GM-CSF proximal promoter, and that the signals impinge on distinct transcription factors that bind to the hCLEO and NF-kappa B regions of the promoter." ], "offsets": [ [ 131, 2379 ] ] } ]

[ { "id": "2856", "type": "DNA_domain_or_region", "text": [ "human granulocyte-macrophage colony-stimulating factor gene promoter" ], "offsets": [ [ 50, 118 ] ], "normalized": [] }, { "id": "2857", "type": "protein_molecule", "text": [ "human granulocyte-macrophage colony-stimulating factor" ], "offsets": [ [ 50, 104 ] ], "normalized": [] }, { "id": "2858", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 122, 129 ] ], "normalized": [] }, { "id": "2859", "type": "DNA_domain_or_region", "text": [ "human granulocyte-macrophage CSF (GM-CSF) gene" ], "offsets": [ [ 135, 181 ] ], "normalized": [] }, { "id": "2860", "type": "protein_molecule", "text": [ "human granulocyte-macrophage CSF" ], "offsets": [ [ 135, 167 ] ], "normalized": [] }, { "id": "2861", "type": "protein_molecule", "text": [ "GM-CSF" ], "offsets": [ [ 169, 175 ] ], "normalized": [] }, { "id": "2862", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 198, 205 ] ], "normalized": [] }, { "id": "2863", "type": "other_name", "text": [ "TCR activation" ], "offsets": [ [ 221, 235 ] ], "normalized": [] }, { "id": "2864", "type": "protein_family_or_group", "text": [ "TCR" ], "offsets": [ [ 221, 224 ] ], "normalized": [] }, { "id": "2865", "type": "other_organic_compound", "text": [ "PMA" ], "offsets": [ [ 288, 291 ] ], "normalized": [] }, { "id": "2866", "type": "other_organic_compound", "text": [ "Ca2+ ionophore" ], "offsets": [ [ 296, 310 ] ], "normalized": [] }, { "id": "2867", "type": "atom", "text": [ "Ca2+" ], "offsets": [ [ 296, 300 ] ], "normalized": [] }, { "id": "2868", "type": "DNA_domain_or_region", "text": [ "proximal functional promoter region" ], "offsets": [ [ 332, 367 ] ], "normalized": [] }, { "id": "2869", "type": "DNA_domain_or_region", "text": [ "-620 to +34" ], "offsets": [ [ 369, 380 ] ], "normalized": [] }, { "id": "2870", "type": "DNA_domain_or_region", "text": [ "enhancer" ], "offsets": [ [ 405, 413 ] ], "normalized": [] }, { "id": "2871", "type": "other_name", "text": [ "TCR activation" ], "offsets": [ [ 495, 509 ] ], "normalized": [] }, { "id": "2872", "type": "protein_family_or_group", "text": [ "TCR" ], "offsets": [ [ 495, 498 ] ], "normalized": [] }, { "id": "2873", "type": "DNA_domain_or_region", "text": [ "proximal promoter" ], "offsets": [ [ 515, 532 ] ], "normalized": [] }, { "id": "2874", "type": "DNA_domain_or_region", "text": [ "CLEO" ], "offsets": [ [ 558, 562 ] ], "normalized": [] }, { "id": "2875", "type": "DNA_domain_or_region", "text": [ "-54 to -31" ], "offsets": [ [ 564, 574 ] ], "normalized": [] }, { "id": "2876", "type": "DNA_domain_or_region", "text": [ "purine-rich element" ], "offsets": [ [ 595, 614 ] ], "normalized": [] }, { "id": "2877", "type": "nucleotide", "text": [ "purine" ], "offsets": [ [ 595, 601 ] ], "normalized": [] }, { "id": "2878", "type": "DNA_domain_or_region", "text": [ "activator protein-1 (AP-1)-like site" ], "offsets": [ [ 627, 663 ] ], "normalized": [] }, { "id": "2879", "type": "protein_molecule", "text": [ "activator protein-1" ], "offsets": [ [ 627, 646 ] ], "normalized": [] }, { "id": "2880", "type": "protein_molecule", "text": [ "AP-1" ], "offsets": [ [ 648, 652 ] ], "normalized": [] }, { "id": "2881", "type": "DNA_domain_or_region", "text": [ "upstream nuclear factor-kappa B (NF-kappa B) site" ], "offsets": [ [ 679, 728 ] ], "normalized": [] }, { "id": "2882", "type": "protein_molecule", "text": [ "nuclear factor-kappa B" ], "offsets": [ [ 688, 710 ] ], "normalized": [] }, { "id": "2883", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 712, 722 ] ], "normalized": [] }, { "id": "2884", "type": "DNA_domain_or_region", "text": [ "-85 to -76" ], "offsets": [ [ 730, 740 ] ], "normalized": [] }, { "id": "2885", "type": "DNA_domain_or_region", "text": [ "CK-1 element" ], "offsets": [ [ 748, 760 ] ], "normalized": [] }, { "id": "2886", "type": "DNA_domain_or_region", "text": [ "-101 to -92" ], "offsets": [ [ 762, 773 ] ], "normalized": [] }, { "id": "2887", "type": "DNA_domain_or_region", "text": [ "purine-rich region" ], "offsets": [ [ 826, 844 ] ], "normalized": [] }, { "id": "2888", "type": "nucleotide", "text": [ "purine" ], "offsets": [ [ 826, 832 ] ], "normalized": [] }, { "id": "2889", "type": "DNA_domain_or_region", "text": [ "CLEO element" ], "offsets": [ [ 852, 864 ] ], "normalized": [] }, { "id": "2890", "type": "DNA_domain_or_region", "text": [ "CLEO" ], "offsets": [ [ 852, 856 ] ], "normalized": [] }, { "id": "2891", "type": "DNA_domain_or_region", "text": [ "NF-kappa B site" ], "offsets": [ [ 872, 887 ] ], "normalized": [] }, { "id": "2892", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 872, 882 ] ], "normalized": [] }, { "id": "2893", "type": "other_organic_compound", "text": [ "PMA" ], "offsets": [ [ 906, 909 ] ], "normalized": [] }, { "id": "2894", "type": "other_name", "text": [ "Ca2+ activation" ], "offsets": [ [ 910, 925 ] ], "normalized": [] }, { "id": "2895", "type": "atom", "text": [ "Ca2+" ], "offsets": [ [ 910, 914 ] ], "normalized": [] }, { "id": "2896", "type": "DNA_molecule", "text": [ "620-bp human GM-CSF promoter-luciferase reporter construct" ], "offsets": [ [ 931, 989 ] ], "normalized": [] }, { "id": "2897", "type": "protein_molecule", "text": [ "GM-CSF" ], "offsets": [ [ 944, 950 ] ], "normalized": [] }, { "id": "2898", "type": "protein_molecule", "text": [ "luciferase" ], "offsets": [ [ 960, 970 ] ], "normalized": [] }, { "id": "2899", "type": "cell_line", "text": [ "Jurkat T cells" ], "offsets": [ [ 993, 1007 ] ], "normalized": [] }, { "id": "2900", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 1000, 1007 ] ], "normalized": [] }, { "id": "2901", "type": "protein_complex", "text": [ "inducible protein complex" ], "offsets": [ [ 1048, 1073 ] ], "normalized": [] }, { "id": "2902", "type": "DNA_domain_or_region", "text": [ "human CLEO (hCLEO) element" ], "offsets": [ [ 1092, 1118 ] ], "normalized": [] }, { "id": "2903", "type": "DNA_domain_or_region", "text": [ "CLEO" ], "offsets": [ [ 1098, 1102 ] ], "normalized": [] }, { "id": "2904", "type": "DNA_domain_or_region", "text": [ "hCLEO" ], "offsets": [ [ 1104, 1109 ] ], "normalized": [] }, { "id": "2905", "type": "protein_complex", "text": [ "AP-1-like complex" ], "offsets": [ [ 1125, 1142 ] ], "normalized": [] }, { "id": "2906", "type": "protein_molecule", "text": [ "AP-1" ], "offsets": [ [ 1125, 1129 ] ], "normalized": [] }, { "id": "2907", "type": "other_organic_compound", "text": [ "PMA" ], "offsets": [ [ 1164, 1167 ] ], "normalized": [] }, { "id": "2908", "type": "other_organic_compound", "text": [ "PMA" ], "offsets": [ [ 1218, 1221 ] ], "normalized": [] }, { "id": "2909", "type": "other_organic_compound", "text": [ "Ca2+ ionophore" ], "offsets": [ [ 1236, 1250 ] ], "normalized": [] }, { "id": "2910", "type": "atom", "text": [ "Ca2+" ], "offsets": [ [ 1236, 1240 ] ], "normalized": [] }, { "id": "2911", "type": "other_name", "text": [ "cyclosporin-sensitive" ], "offsets": [ [ 1296, 1317 ] ], "normalized": [] }, { "id": "2912", "type": "other_organic_compound", "text": [ "cyclosporin" ], "offsets": [ [ 1296, 1307 ] ], "normalized": [] }, { "id": "2913", "type": "other_name", "text": [ "promoter induction" ], "offsets": [ [ 1319, 1337 ] ], "normalized": [] }, { "id": "2914", "type": "other_name", "text": [ "cyclosporin treatment" ], "offsets": [ [ 1354, 1375 ] ], "normalized": [] }, { "id": "2915", "type": "other_organic_compound", "text": [ "cyclosporin" ], "offsets": [ [ 1354, 1365 ] ], "normalized": [] }, { "id": "2916", "type": "protein_family_or_group", "text": [ "nuclear factor of activated T cells" ], "offsets": [ [ 1420, 1455 ] ], "normalized": [] }, { "id": "2917", "type": "protein_family_or_group", "text": [ "NF-AT" ], "offsets": [ [ 1457, 1462 ] ], "normalized": [] }, { "id": "2918", "type": "DNA_domain_or_region", "text": [ "hCLEO region" ], "offsets": [ [ 1497, 1509 ] ], "normalized": [] }, { "id": "2919", "type": "DNA_domain_or_region", "text": [ "hCLEO" ], "offsets": [ [ 1497, 1502 ] ], "normalized": [] }, { "id": "2920", "type": "protein_family_or_group", "text": [ "recombinant proteins" ], "offsets": [ [ 1520, 1540 ] ], "normalized": [] }, { "id": "2921", "type": "protein_molecule", "text": [ "AP-1" ], "offsets": [ [ 1560, 1564 ] ], "normalized": [] }, { "id": "2922", "type": "protein_molecule", "text": [ "NF-ATp" ], "offsets": [ [ 1566, 1572 ] ], "normalized": [] }, { "id": "2923", "type": "protein_complex", "text": [ "NF-ATp/AP-1 complex" ], "offsets": [ [ 1593, 1612 ] ], "normalized": [] }, { "id": "2924", "type": "protein_molecule", "text": [ "NF-ATp" ], "offsets": [ [ 1593, 1599 ] ], "normalized": [] }, { "id": "2925", "type": "protein_molecule", "text": [ "AP-1" ], "offsets": [ [ 1600, 1604 ] ], "normalized": [] }, { "id": "2926", "type": "DNA_domain_or_region", "text": [ "hCLEO element" ], "offsets": [ [ 1637, 1650 ] ], "normalized": [] }, { "id": "2927", "type": "DNA_domain_or_region", "text": [ "hCLEO" ], "offsets": [ [ 1637, 1642 ] ], "normalized": [] }, { "id": "2928", "type": "protein_molecule", "text": [ "calcineurin" ], "offsets": [ [ 1803, 1814 ] ], "normalized": [] }, { "id": "2929", "type": "other_organic_compound", "text": [ "Ca2+ ionophore" ], "offsets": [ [ 1836, 1850 ] ], "normalized": [] }, { "id": "2930", "type": "atom", "text": [ "Ca2+" ], "offsets": [ [ 1836, 1840 ] ], "normalized": [] }, { "id": "2931", "type": "other_organic_compound", "text": [ "PMA" ], "offsets": [ [ 1870, 1873 ] ], "normalized": [] }, { "id": "2932", "type": "DNA_domain_or_region", "text": [ "GM-CSF promoter" ], "offsets": [ [ 1890, 1905 ] ], "normalized": [] }, { "id": "2933", "type": "protein_molecule", "text": [ "GM-CSF" ], "offsets": [ [ 1890, 1896 ] ], "normalized": [] }, { "id": "2934", "type": "protein_molecule", "text": [ "mutant-activated Ras" ], "offsets": [ [ 1927, 1947 ] ], "normalized": [] }, { "id": "2935", "type": "other_organic_compound", "text": [ "PMA" ], "offsets": [ [ 1969, 1972 ] ], "normalized": [] }, { "id": "2936", "type": "other_organic_compound", "text": [ "Ca2+ ionophore" ], "offsets": [ [ 1992, 2006 ] ], "normalized": [] }, { "id": "2937", "type": "atom", "text": [ "Ca2+" ], "offsets": [ [ 1992, 1996 ] ], "normalized": [] }, { "id": "2938", "type": "protein_molecule", "text": [ "Ras" ], "offsets": [ [ 2025, 2028 ] ], "normalized": [] }, { "id": "2939", "type": "protein_molecule", "text": [ "calcineurin" ], "offsets": [ [ 2033, 2044 ] ], "normalized": [] }, { "id": "2940", "type": "DNA_domain_or_region", "text": [ "GM-CSF promoter" ], "offsets": [ [ 2076, 2091 ] ], "normalized": [] }, { "id": "2941", "type": "protein_molecule", "text": [ "GM-CSF" ], "offsets": [ [ 2076, 2082 ] ], "normalized": [] }, { "id": "2942", "type": "protein_subunit", "text": [ "NF-kappa B p65" ], "offsets": [ [ 2135, 2149 ] ], "normalized": [] }, { "id": "2943", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 2135, 2145 ] ], "normalized": [] }, { "id": "2944", "type": "DNA_domain_or_region", "text": [ "GM-CSF proximal promoter" ], "offsets": [ [ 2228, 2252 ] ], "normalized": [] }, { "id": "2945", "type": "protein_molecule", "text": [ "GM-CSF" ], "offsets": [ [ 2228, 2234 ] ], "normalized": [] }, { "id": "2946", "type": "DNA_domain_or_region", "text": [ "proximal promoter" ], "offsets": [ [ 2235, 2252 ] ], "normalized": [] }, { "id": "2947", "type": "protein_family_or_group", "text": [ "transcription factors" ], "offsets": [ [ 2295, 2316 ] ], "normalized": [] }, { "id": "2948", "type": "DNA_domain_or_region", "text": [ "hCLEO and NF-kappa B regions" ], "offsets": [ [ 2334, 2362 ] ], "normalized": [] }, { "id": "2949", "type": "DNA_domain_or_region", "text": [ "hCLEO" ], "offsets": [ [ 2334, 2339 ] ], "normalized": [] }, { "id": "2950", "type": "DNA_domain_or_region", "text": [ "hCLEO" ], "offsets": [ [ 2334, 2339 ] ], "normalized": [] }, { "id": "2951", "type": "DNA_domain_or_region", "text": [ "NF-kappa B regions" ], "offsets": [ [ 2344, 2362 ] ], "normalized": [] }, { "id": "2952", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 2344, 2354 ] ], "normalized": [] }, { "id": "2953", "type": "DNA_domain_or_region", "text": [ "promoter" ], "offsets": [ [ 2244, 2252 ] ], "normalized": [] } ]

[]

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[]

[ { "id": "2955", "type": "title", "text": [ "IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 and the differential assembly of STAT1 alpha and STAT3 complexes in human T cells and monocytes." ], "offsets": [ [ 0, 156 ] ] }, { "id": "2956", "type": "abstract", "text": [ "IL-10 affects monocytes and T cells by driving the progression of immune responsiveness such that Th2 lymphocyte-mediated effects predominate. In this report, we show that in monocytes and T cells IL-10 stimulates tyrosine phosphorylation of the signal transducers and activators of transcription, STAT1 alpha and STAT3, in a differential manner such that the relative formation of homo- and heterodimers varies between the two cell types. Moreover, monocytes express a novel IL-10-stimulated STAT protein with an M(r) of 70 kDa that is recognized by the anti-STAT3 Ab but is not observed in T cells. IL-10 treatment of both T cells and monocytes results in the ligand-induced tyrosine phosphorylation of tyk2 and Jak1, but not Jak2 or Jak3. Selective modulation of immune responsiveness by IL-10 in cells such as monocytes and T cells may result in part from the differential activation of STAT protein pairs." ], "offsets": [ [ 157, 1067 ] ] } ]

[ { "id": "2957", "type": "other_name", "text": [ "tyrosine phosphorylation" ], "offsets": [ [ 18, 42 ] ], "normalized": [] }, { "id": "2958", "type": "amino_acid_monomer", "text": [ "tyrosine" ], "offsets": [ [ 18, 26 ] ], "normalized": [] }, { "id": "2959", "type": "protein_molecule", "text": [ "tyk2" ], "offsets": [ [ 46, 50 ] ], "normalized": [] }, { "id": "2960", "type": "protein_molecule", "text": [ "Jak1" ], "offsets": [ [ 55, 59 ] ], "normalized": [] }, { "id": "2961", "type": "protein_molecule", "text": [ "STAT1 alpha" ], "offsets": [ [ 93, 104 ] ], "normalized": [] }, { "id": "2962", "type": "protein_complex", "text": [ "STAT3 complexes" ], "offsets": [ [ 109, 124 ] ], "normalized": [] }, { "id": "2963", "type": "cell_type", "text": [ "human T cells" ], "offsets": [ [ 128, 141 ] ], "normalized": [] }, { "id": "2964", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 146, 155 ] ], "normalized": [] }, { "id": "2965", "type": "protein_molecule", "text": [ "IL-10" ], "offsets": [ [ 157, 162 ] ], "normalized": [] }, { "id": "2966", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 171, 180 ] ], "normalized": [] }, { "id": "2967", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 185, 192 ] ], "normalized": [] }, { "id": "2968", "type": "other_name", "text": [ "immune responsiveness" ], "offsets": [ [ 223, 244 ] ], "normalized": [] }, { "id": "2969", "type": "other_name", "text": [ "Th2 lymphocyte-mediated effects" ], "offsets": [ [ 255, 286 ] ], "normalized": [] }, { "id": "2970", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 332, 341 ] ], "normalized": [] }, { "id": "2971", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 346, 353 ] ], "normalized": [] }, { "id": "2972", "type": "protein_molecule", "text": [ "IL-10" ], "offsets": [ [ 354, 359 ] ], "normalized": [] }, { "id": "2973", "type": "other_name", "text": [ "tyrosine phosphorylation" ], "offsets": [ [ 371, 395 ] ], "normalized": [] }, { "id": "2974", "type": "amino_acid_monomer", "text": [ "tyrosine" ], "offsets": [ [ 371, 379 ] ], "normalized": [] }, { "id": "2975", "type": "protein_family_or_group", "text": [ "signal transducers" ], "offsets": [ [ 403, 421 ] ], "normalized": [] }, { "id": "2976", "type": "protein_family_or_group", "text": [ "activators of transcription" ], "offsets": [ [ 426, 453 ] ], "normalized": [] }, { "id": "2977", "type": "protein_molecule", "text": [ "STAT1 alpha" ], "offsets": [ [ 455, 466 ] ], "normalized": [] }, { "id": "2978", "type": "protein_molecule", "text": [ "STAT3" ], "offsets": [ [ 471, 476 ] ], "normalized": [] }, { "id": "2979", "type": "(AND protein_family_or_group protein_family_or_group)", "text": [ "homo- and heterodimers" ], "offsets": [ [ 539, 561 ] ], "normalized": [] }, { "id": "2980", "type": "", "text": [ "homo-" ], "offsets": [ [ 539, 544 ] ], "normalized": [] }, { "id": "2981", "type": "", "text": [ "hetero" ], "offsets": [ [ 549, 555 ] ], "normalized": [] }, { "id": "2982", "type": "", "text": [ "dimers" ], "offsets": [ [ 555, 561 ] ], "normalized": [] }, { "id": "2983", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 607, 616 ] ], "normalized": [] }, { "id": "2984", "type": "protein_molecule", "text": [ "IL-10-stimulated STAT protein" ], "offsets": [ [ 633, 662 ] ], "normalized": [] }, { "id": "2985", "type": "protein_molecule", "text": [ "IL-10" ], "offsets": [ [ 633, 638 ] ], "normalized": [] }, { "id": "2986", "type": "protein_molecule", "text": [ "70 kDa" ], "offsets": [ [ 679, 685 ] ], "normalized": [] }, { "id": "2987", "type": "protein_family_or_group", "text": [ "anti-STAT3 Ab" ], "offsets": [ [ 712, 725 ] ], "normalized": [] }, { "id": "2988", "type": "protein_molecule", "text": [ "STAT3" ], "offsets": [ [ 717, 722 ] ], "normalized": [] }, { "id": "2989", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 749, 756 ] ], "normalized": [] }, { "id": "2990", "type": "protein_molecule", "text": [ "IL-10" ], "offsets": [ [ 758, 763 ] ], "normalized": [] }, { "id": "2991", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 782, 789 ] ], "normalized": [] }, { "id": "2992", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 794, 803 ] ], "normalized": [] }, { "id": "2993", "type": "other_name", "text": [ "ligand-induced tyrosine phosphorylation" ], "offsets": [ [ 819, 858 ] ], "normalized": [] }, { "id": "2994", "type": "other_name", "text": [ "tyrosine phosphorylation" ], "offsets": [ [ 834, 858 ] ], "normalized": [] }, { "id": "2995", "type": "amino_acid_monomer", "text": [ "tyrosine" ], "offsets": [ [ 834, 842 ] ], "normalized": [] }, { "id": "2996", "type": "protein_molecule", "text": [ "tyk2" ], "offsets": [ [ 862, 866 ] ], "normalized": [] }, { "id": "2997", "type": "protein_molecule", "text": [ "Jak1" ], "offsets": [ [ 871, 875 ] ], "normalized": [] }, { "id": "2998", "type": "protein_molecule", "text": [ "Jak2" ], "offsets": [ [ 885, 889 ] ], "normalized": [] }, { "id": "2999", "type": "protein_molecule", "text": [ "Jak3" ], "offsets": [ [ 893, 897 ] ], "normalized": [] }, { "id": "3000", "type": "other_name", "text": [ "immune responsiveness" ], "offsets": [ [ 923, 944 ] ], "normalized": [] }, { "id": "3001", "type": "protein_molecule", "text": [ "IL-10" ], "offsets": [ [ 948, 953 ] ], "normalized": [] }, { "id": "3002", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 971, 980 ] ], "normalized": [] }, { "id": "3003", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 985, 992 ] ], "normalized": [] }, { "id": "3004", "type": "other_name", "text": [ "differential activation" ], "offsets": [ [ 1021, 1044 ] ], "normalized": [] }, { "id": "3005", "type": "protein_family_or_group", "text": [ "STAT protein pairs" ], "offsets": [ [ 1048, 1066 ] ], "normalized": [] } ]

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[ { "id": "3007", "type": "title", "text": [ "Use of new biologic markers in the ovulation induction." ], "offsets": [ [ 0, 55 ] ] }, { "id": "3008", "type": "abstract", "text": [ "Biological markers of ovulation, after a great in the past, have been fallen into disuse for the large diffusion of biochemical and biophysical ones. However, the real effect of hormones involved in ovulation is expressed by biological modifications on target tissues. To explore the modifications of not reproductive target tissues as ovulation markers we studied the behaviour of Albuminemia, Platelet Factor IV (as indicator of Platelet Aggregation), Type II estrogenic receptors in 42 ovulation induced women, undergoing our observation. 33 of them had ovulation and 9 developed a LUF syndrome, constituting two biological models of an opposite situation for the three markers observed. All the markers considered were sufficiently sensitive, but among them, Platelet Factor IV was the most reliable to the hormonal ovulatory situation." ], "offsets": [ [ 56, 896 ] ] } ]

[ { "id": "3009", "type": "other_name", "text": [ "biologic markers" ], "offsets": [ [ 11, 27 ] ], "normalized": [] }, { "id": "3010", "type": "other_name", "text": [ "ovulation induction" ], "offsets": [ [ 35, 54 ] ], "normalized": [] }, { "id": "3011", "type": "other_name", "text": [ "Biological markers of ovulation" ], "offsets": [ [ 56, 87 ] ], "normalized": [] }, { "id": "3012", "type": "other_organic_compound", "text": [ "hormones" ], "offsets": [ [ 234, 242 ] ], "normalized": [] }, { "id": "3013", "type": "other_name", "text": [ "ovulation" ], "offsets": [ [ 255, 264 ] ], "normalized": [] }, { "id": "3014", "type": "other_name", "text": [ "biological modifications" ], "offsets": [ [ 281, 305 ] ], "normalized": [] }, { "id": "3015", "type": "cell_type", "text": [ "target tissues" ], "offsets": [ [ 309, 323 ] ], "normalized": [] }, { "id": "3016", "type": "other_name", "text": [ "Albuminemia" ], "offsets": [ [ 438, 449 ] ], "normalized": [] }, { "id": "3017", "type": "protein_molecule", "text": [ "Platelet Factor IV" ], "offsets": [ [ 451, 469 ] ], "normalized": [] }, { "id": "3018", "type": "other_name", "text": [ "Platelet Aggregation" ], "offsets": [ [ 487, 507 ] ], "normalized": [] }, { "id": "3019", "type": "protein_family_or_group", "text": [ "Type II estrogenic receptors" ], "offsets": [ [ 510, 538 ] ], "normalized": [] }, { "id": "3020", "type": "multi_cell", "text": [ "ovulation induced women" ], "offsets": [ [ 545, 568 ] ], "normalized": [] }, { "id": "3021", "type": "other_name", "text": [ "ovulation" ], "offsets": [ [ 613, 622 ] ], "normalized": [] }, { "id": "3022", "type": "other_name", "text": [ "LUF syndrome" ], "offsets": [ [ 641, 653 ] ], "normalized": [] }, { "id": "3023", "type": "protein_molecule", "text": [ "Platelet Factor IV" ], "offsets": [ [ 819, 837 ] ], "normalized": [] }, { "id": "3024", "type": "other_name", "text": [ "hormonal ovulatory situation" ], "offsets": [ [ 867, 895 ] ], "normalized": [] } ]

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[ { "id": "3026", "type": "title", "text": [ "Abnormal regulation of the IL-2 promoter in lpr CD4-CD8- T lymphocytes results in constitutive expression of a novel nuclear factor of activated T cells-binding factor." ], "offsets": [ [ 0, 168 ] ] }, { "id": "3027", "type": "abstract", "text": [ "The inert quality of MRL-Ipr/Ipr (Ipr) peripheral CD4-CD8- (CD4-8-) T cells manifests primarily as an inability to proliferate or produce IL-2 in response to TCR or mitogenic stimulation. Yet these same cells do initiate early TCR-mediated signaling events, such as generation of inositol phosphates and increased intracellular calcium. They also display constitutively high levels of p59fyn and CD3 zeta tyrosine phosphorylation. The generation of second messengers in T cells normally leads to downstream signaling that results in transcriptional activation of the IL-2 gene. We, therefore, compared the activation state of the IL-2 gene promoter region in freshly isolated and stimulated Ipr CD4-8- T cells with that of normal T lymphocytes. Levels of the octamer, NF-kappa B (p50-p65 heterodimer), and AP-1 transcriptional factors are constitutively elevated in freshly isolated Ipr CD4-8- T cells, consistent with the activated phenotype of these cells. Upon stimulation with mitogens, formation of the transactivating complex, nuclear factor of activated T cells (NF-AT), occurs with normal kinetics in Ipr CD4-8- T cells. Yet, the levels of the activating NF-AT complex never reach those observed in similarly stimulated normal T cells. Furthermore, nuclear extracts from Ipr CD4-8- T cells display high levels of a novel specific binding activity at the NF-AT site, which is present at much lower levels in freshly isolated normal T lymphocytes. Upon mitogenic stimulation, the binding activity of the novel NF-AT-binding factor is rapidly down-regulated in normal T cells, but persists at high levels in Ipr CD4-8- T cells. These two abnormalities at the NF-AT site provide a potential mechanism to account for the defect in IL-2 production from Ipr CD4-8- T cells." ], "offsets": [ [ 169, 1943 ] ] } ]

[ { "id": "3028", "type": "DNA_domain_or_region", "text": [ "IL-2 promoter" ], "offsets": [ [ 27, 40 ] ], "normalized": [] }, { "id": "3029", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 27, 31 ] ], "normalized": [] }, { "id": "3030", "type": "cell_line", "text": [ "CD4-CD8- T lymphocytes" ], "offsets": [ [ 48, 70 ] ], "normalized": [] }, { "id": "3031", "type": "other_name", "text": [ "constitutive expression" ], "offsets": [ [ 82, 105 ] ], "normalized": [] }, { "id": "3032", "type": "protein_family_or_group", "text": [ "novel nuclear factor of activated T cells-binding factor" ], "offsets": [ [ 111, 167 ] ], "normalized": [] }, { "id": "3033", "type": "protein_family_or_group", "text": [ "nuclear factor of activated T cells" ], "offsets": [ [ 117, 152 ] ], "normalized": [] }, { "id": "3034", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 145, 152 ] ], "normalized": [] }, { "id": "3035", "type": "cell_line", "text": [ "MRL-Ipr/Ipr (Ipr) peripheral CD4-CD8- (CD4-8-) T cells" ], "offsets": [ [ 190, 244 ] ], "normalized": [] }, { "id": "3036", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 237, 244 ] ], "normalized": [] }, { "id": "3037", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 307, 311 ] ], "normalized": [] }, { "id": "3038", "type": "protein_family_or_group", "text": [ "TCR" ], "offsets": [ [ 327, 330 ] ], "normalized": [] }, { "id": "3039", "type": "other_name", "text": [ "mitogenic stimulation" ], "offsets": [ [ 334, 355 ] ], "normalized": [] }, { "id": "3040", "type": "other_name", "text": [ "early TCR-mediated signaling events" ], "offsets": [ [ 390, 425 ] ], "normalized": [] }, { "id": "3041", "type": "protein_family_or_group", "text": [ "TCR" ], "offsets": [ [ 396, 399 ] ], "normalized": [] }, { "id": "3042", "type": "other_organic_compound", "text": [ "inositol phosphates" ], "offsets": [ [ 449, 468 ] ], "normalized": [] }, { "id": "3043", "type": "atom", "text": [ "intracellular calcium" ], "offsets": [ [ 483, 504 ] ], "normalized": [] }, { "id": "3044", "type": "atom", "text": [ "calcium" ], "offsets": [ [ 497, 504 ] ], "normalized": [] }, { "id": "3045", "type": "protein_molecule", "text": [ "p59fyn" ], "offsets": [ [ 554, 560 ] ], "normalized": [] }, { "id": "3046", "type": "protein_molecule", "text": [ "CD3 zeta" ], "offsets": [ [ 565, 573 ] ], "normalized": [] }, { "id": "3047", "type": "other_name", "text": [ "tyrosine phosphorylation" ], "offsets": [ [ 574, 598 ] ], "normalized": [] }, { "id": "3048", "type": "amino_acid_monomer", "text": [ "tyrosine" ], "offsets": [ [ 574, 582 ] ], "normalized": [] }, { "id": "3049", "type": "other_organic_compound", "text": [ "second messengers" ], "offsets": [ [ 618, 635 ] ], "normalized": [] }, { "id": "3050", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 639, 646 ] ], "normalized": [] }, { "id": "3051", "type": "other_name", "text": [ "downstream signaling" ], "offsets": [ [ 665, 685 ] ], "normalized": [] }, { "id": "3052", "type": "other_name", "text": [ "transcriptional activation" ], "offsets": [ [ 702, 728 ] ], "normalized": [] }, { "id": "3053", "type": "DNA_domain_or_region", "text": [ "IL-2 gene" ], "offsets": [ [ 736, 745 ] ], "normalized": [] }, { "id": "3054", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 736, 740 ] ], "normalized": [] }, { "id": "3055", "type": "DNA_domain_or_region", "text": [ "IL-2 gene promoter region" ], "offsets": [ [ 799, 824 ] ], "normalized": [] }, { "id": "3056", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 799, 803 ] ], "normalized": [] }, { "id": "3057", "type": "cell_line", "text": [ "Ipr CD4-8- T cells" ], "offsets": [ [ 860, 878 ] ], "normalized": [] }, { "id": "3058", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 871, 878 ] ], "normalized": [] }, { "id": "3059", "type": "cell_type", "text": [ "normal T lymphocytes" ], "offsets": [ [ 892, 912 ] ], "normalized": [] }, { "id": "3060", "type": "polynucleotide", "text": [ "octamer" ], "offsets": [ [ 928, 935 ] ], "normalized": [] }, { "id": "3061", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 937, 947 ] ], "normalized": [] }, { "id": "3062", "type": "protein_molecule", "text": [ "p50-p65 heterodimer" ], "offsets": [ [ 949, 968 ] ], "normalized": [] }, { "id": "3063", "type": "protein_family_or_group", "text": [ "AP-1 transcriptional factors" ], "offsets": [ [ 975, 1003 ] ], "normalized": [] }, { "id": "3064", "type": "protein_molecule", "text": [ "AP-1" ], "offsets": [ [ 975, 979 ] ], "normalized": [] }, { "id": "3065", "type": "cell_line", "text": [ "Ipr CD4-8- T cells" ], "offsets": [ [ 1052, 1070 ] ], "normalized": [] }, { "id": "3066", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 1063, 1070 ] ], "normalized": [] }, { "id": "3067", "type": "other_organic_compound", "text": [ "mitogens" ], "offsets": [ [ 1150, 1158 ] ], "normalized": [] }, { "id": "3068", "type": "protein_family_or_group", "text": [ "nuclear factor of activated T cells" ], "offsets": [ [ 1202, 1237 ] ], "normalized": [] }, { "id": "3069", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 1230, 1237 ] ], "normalized": [] }, { "id": "3070", "type": "protein_family_or_group", "text": [ "NF-AT" ], "offsets": [ [ 1239, 1244 ] ], "normalized": [] }, { "id": "3071", "type": "cell_line", "text": [ "Ipr CD4-8- T cells" ], "offsets": [ [ 1278, 1296 ] ], "normalized": [] }, { "id": "3072", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 1289, 1296 ] ], "normalized": [] }, { "id": "3073", "type": "protein_complex", "text": [ "NF-AT complex" ], "offsets": [ [ 1332, 1345 ] ], "normalized": [] }, { "id": "3074", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 1404, 1411 ] ], "normalized": [] }, { "id": "3075", "type": "cell_component", "text": [ "nuclear extracts" ], "offsets": [ [ 1426, 1442 ] ], "normalized": [] }, { "id": "3076", "type": "cell_line", "text": [ "Ipr CD4-8- T cells" ], "offsets": [ [ 1448, 1466 ] ], "normalized": [] }, { "id": "3077", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 1459, 1466 ] ], "normalized": [] }, { "id": "3078", "type": "other_name", "text": [ "novel specific binding activity" ], "offsets": [ [ 1492, 1523 ] ], "normalized": [] }, { "id": "3079", "type": "DNA_domain_or_region", "text": [ "NF-AT site" ], "offsets": [ [ 1531, 1541 ] ], "normalized": [] }, { "id": "3080", "type": "protein_family_or_group", "text": [ "NF-AT" ], "offsets": [ [ 1531, 1536 ] ], "normalized": [] }, { "id": "3081", "type": "cell_type", "text": [ "normal T lymphocytes" ], "offsets": [ [ 1601, 1621 ] ], "normalized": [] }, { "id": "3082", "type": "other_name", "text": [ "mitogenic stimulation" ], "offsets": [ [ 1628, 1649 ] ], "normalized": [] }, { "id": "3083", "type": "protein_family_or_group", "text": [ "NF-AT-binding factor" ], "offsets": [ [ 1685, 1705 ] ], "normalized": [] }, { "id": "3084", "type": "protein_family_or_group", "text": [ "NF-AT" ], "offsets": [ [ 1685, 1690 ] ], "normalized": [] }, { "id": "3085", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 1742, 1749 ] ], "normalized": [] }, { "id": "3086", "type": "cell_line", "text": [ "Ipr CD4-8- T cells" ], "offsets": [ [ 1782, 1800 ] ], "normalized": [] }, { "id": "3087", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 1793, 1800 ] ], "normalized": [] }, { "id": "3088", "type": "DNA_domain_or_region", "text": [ "NF-AT site" ], "offsets": [ [ 1833, 1843 ] ], "normalized": [] }, { "id": "3089", "type": "protein_family_or_group", "text": [ "NF-AT" ], "offsets": [ [ 1833, 1838 ] ], "normalized": [] }, { "id": "3090", "type": "other_name", "text": [ "IL-2 production" ], "offsets": [ [ 1903, 1918 ] ], "normalized": [] }, { "id": "3091", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 1903, 1907 ] ], "normalized": [] }, { "id": "3092", "type": "cell_line", "text": [ "Ipr CD4-8- T cells" ], "offsets": [ [ 1924, 1942 ] ], "normalized": [] }, { "id": "3093", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 1935, 1942 ] ], "normalized": [] } ]

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[ { "id": "3095", "type": "title", "text": [ "Cross-linking of CD30 induces HIV expression in chronically infected T cells." ], "offsets": [ [ 0, 77 ] ] }, { "id": "3096", "type": "abstract", "text": [ "CD30, a member of the tumor necrosis factor (TNF) receptor family, is expressed constitutively on the surface of the human T cell line ACH-2, which is chronically infected with human immunodeficiency virus type-1 (HIV)-1. We demonstrate that cross-linking CD30 with an anti-CD30-specific monoclonal antibody, which mimics the described biological activities of the CD30 ligand (CD30L), results in HIV expression. CD30 cross-linking does not alter proliferation of ACH-2 cells and the induction of HIV expression is not mediated by endogenous TNF alpha/beta. Furthermore, cross-linking of CD30 leads to NF-kappa B activation and enhanced HIV transcription. Thus, CD30-CD30L interactions mediate the induction of HIV expression by a kappa B-dependent pathway that is independent of TNF. This mechanism may be important in the activation of HIV expression from latently infected CD4+ T cells, especially in lymphoid organs where cell to cell contact is conducive to receptor-ligand interactions." ], "offsets": [ [ 78, 1070 ] ] } ]

[ { "id": "3097", "type": "protein_molecule", "text": [ "CD30" ], "offsets": [ [ 17, 21 ] ], "normalized": [] }, { "id": "3098", "type": "other_name", "text": [ "HIV expression" ], "offsets": [ [ 30, 44 ] ], "normalized": [] }, { "id": "3099", "type": "virus", "text": [ "HIV" ], "offsets": [ [ 30, 33 ] ], "normalized": [] }, { "id": "3100", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 69, 76 ] ], "normalized": [] }, { "id": "3101", "type": "protein_molecule", "text": [ "CD30" ], "offsets": [ [ 78, 82 ] ], "normalized": [] }, { "id": "3102", "type": "virus", "text": [ "HIV" ], "offsets": [ [ 292, 295 ] ], "normalized": [] }, { "id": "3103", "type": "protein_molecule", "text": [ "CD30" ], "offsets": [ [ 334, 338 ] ], "normalized": [] }, { "id": "3104", "type": "protein_molecule", "text": [ "CD30" ], "offsets": [ [ 352, 356 ] ], "normalized": [] }, { "id": "3105", "type": "protein_molecule", "text": [ "CD30 ligand" ], "offsets": [ [ 443, 454 ] ], "normalized": [] }, { "id": "3106", "type": "protein_molecule", "text": [ "CD30L" ], "offsets": [ [ 456, 461 ] ], "normalized": [] }, { "id": "3107", "type": "other_name", "text": [ "HIV expression" ], "offsets": [ [ 475, 489 ] ], "normalized": [] }, { "id": "3108", "type": "virus", "text": [ "HIV" ], "offsets": [ [ 475, 478 ] ], "normalized": [] }, { "id": "3109", "type": "protein_molecule", "text": [ "CD30" ], "offsets": [ [ 491, 495 ] ], "normalized": [] }, { "id": "3110", "type": "cell_line", "text": [ "ACH-2 cells" ], "offsets": [ [ 542, 553 ] ], "normalized": [] }, { "id": "3111", "type": "other_name", "text": [ "HIV expression" ], "offsets": [ [ 575, 589 ] ], "normalized": [] }, { "id": "3112", "type": "virus", "text": [ "HIV" ], "offsets": [ [ 575, 578 ] ], "normalized": [] }, { "id": "3113", "type": "protein_molecule", "text": [ "TNF alpha/beta" ], "offsets": [ [ 620, 634 ] ], "normalized": [] }, { "id": "3114", "type": "protein_molecule", "text": [ "CD30" ], "offsets": [ [ 666, 670 ] ], "normalized": [] }, { "id": "3115", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 680, 690 ] ], "normalized": [] }, { "id": "3116", "type": "other_name", "text": [ "HIV transcription" ], "offsets": [ [ 715, 732 ] ], "normalized": [] }, { "id": "3117", "type": "virus", "text": [ "HIV" ], "offsets": [ [ 715, 718 ] ], "normalized": [] }, { "id": "3118", "type": "other_name", "text": [ "CD30-CD30L interactions" ], "offsets": [ [ 740, 763 ] ], "normalized": [] }, { "id": "3119", "type": "protein_molecule", "text": [ "CD30" ], "offsets": [ [ 740, 744 ] ], "normalized": [] }, { "id": "3120", "type": "protein_molecule", "text": [ "-CD30L" ], "offsets": [ [ 744, 750 ] ], "normalized": [] }, { "id": "3121", "type": "other_name", "text": [ "HIV expression" ], "offsets": [ [ 789, 803 ] ], "normalized": [] }, { "id": "3122", "type": "virus", "text": [ "HIV" ], "offsets": [ [ 789, 792 ] ], "normalized": [] }, { "id": "3123", "type": "other_name", "text": [ "kappa B-dependent pathway" ], "offsets": [ [ 809, 834 ] ], "normalized": [] }, { "id": "3124", "type": "protein_family_or_group", "text": [ "TNF" ], "offsets": [ [ 858, 861 ] ], "normalized": [] }, { "id": "3125", "type": "other_name", "text": [ "HIV expression" ], "offsets": [ [ 916, 930 ] ], "normalized": [] }, { "id": "3126", "type": "virus", "text": [ "HIV" ], "offsets": [ [ 916, 919 ] ], "normalized": [] }, { "id": "3127", "type": "cell_line", "text": [ "CD4+ T cells" ], "offsets": [ [ 954, 966 ] ], "normalized": [] }, { "id": "3128", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 959, 966 ] ], "normalized": [] }, { "id": "3129", "type": "body_part", "text": [ "lymphoid organs" ], "offsets": [ [ 982, 997 ] ], "normalized": [] }, { "id": "3130", "type": "other_name", "text": [ "cell to cell contact" ], "offsets": [ [ 1004, 1024 ] ], "normalized": [] }, { "id": "3131", "type": "other_name", "text": [ "receptor-ligand interactions" ], "offsets": [ [ 1041, 1069 ] ], "normalized": [] } ]

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[ { "id": "3133", "type": "title", "text": [ "Human MHC class II gene transcription directed by the carboxyl terminus of CIITA, one of the defective genes in type II MHC combined immune deficiency." ], "offsets": [ [ 0, 151 ] ] }, { "id": "3134", "type": "abstract", "text": [ "Type II major histocompatibility complex combined immune deficiency (type II MHC CID or bare lymphocyte syndrome) is a congenital immunodeficiency disease characterized by absent MHC class II expression. Four distinct complementation groups have been identified. Recently, the defective gene in group II type II MHC CID has been isolated and termed CIITA. Here, we demonstrate that CIITA is an MHC class II gene-specific transcription activator. The transcription activation function is provided by the N-terminal acidic domain (amino acids 26-137), which is experimentally exchangeable with a heterologous viral transcription-activating domain. The specificity of CIITA for three major MHC class II genes, DR, DQ and DP, is mediated by its remaining C-terminal residues (amino acids 317-1130). The transactivation of multiple cis elements, especially S and X2, of the DR alpha proximal promoter in group II CID cells is CIITA dependent. Since CIITA overexpression in normal cells did not increase class II expression, we propose that initiation of CIITA expression serves as the on-off switch, while availability of downstream interactor(s) limits transcription." ], "offsets": [ [ 152, 1315 ] ] } ]

[ { "id": "3135", "type": "other_name", "text": [ "Human MHC class II gene transcription" ], "offsets": [ [ 0, 37 ] ], "normalized": [] }, { "id": "3136", "type": "DNA_family_or_group", "text": [ "MHC class II gene" ], "offsets": [ [ 6, 23 ] ], "normalized": [] }, { "id": "3137", "type": "protein_domain_or_region", "text": [ "carboxyl terminus" ], "offsets": [ [ 54, 71 ] ], "normalized": [] }, { "id": "3138", "type": "DNA_domain_or_region", "text": [ "CIITA" ], "offsets": [ [ 75, 80 ] ], "normalized": [] }, { "id": "3139", "type": "DNA_family_or_group", "text": [ "defective genes" ], "offsets": [ [ 93, 108 ] ], "normalized": [] }, { "id": "3140", "type": "other_name", "text": [ "II MHC combined immune deficiency" ], "offsets": [ [ 117, 150 ] ], "normalized": [] }, { "id": "3141", "type": "protein_complex", "text": [ "MHC" ], "offsets": [ [ 6, 9 ] ], "normalized": [] }, { "id": "3142", "type": "other_name", "text": [ "Type II major histocompatibility complex combined immune deficiency" ], "offsets": [ [ 152, 219 ] ], "normalized": [] }, { "id": "3143", "type": "protein_complex", "text": [ "Type II major histocompatibility complex" ], "offsets": [ [ 152, 192 ] ], "normalized": [] }, { "id": "3144", "type": "other_name", "text": [ "type II MHC CID" ], "offsets": [ [ 221, 236 ] ], "normalized": [] }, { "id": "3145", "type": "protein_complex", "text": [ "MHC" ], "offsets": [ [ 229, 232 ] ], "normalized": [] }, { "id": "3146", "type": "other_name", "text": [ "bare lymphocyte syndrome" ], "offsets": [ [ 240, 264 ] ], "normalized": [] }, { "id": "3147", "type": "other_name", "text": [ "MHC class II expression" ], "offsets": [ [ 331, 354 ] ], "normalized": [] }, { "id": "3148", "type": "protein_complex", "text": [ "MHC class II" ], "offsets": [ [ 331, 343 ] ], "normalized": [] }, { "id": "3149", "type": "DNA_family_or_group", "text": [ "defective gene" ], "offsets": [ [ 429, 443 ] ], "normalized": [] }, { "id": "3150", "type": "other_name", "text": [ "group II type II MHC CID" ], "offsets": [ [ 447, 471 ] ], "normalized": [] }, { "id": "3151", "type": "other_name", "text": [ "type II MHC CID" ], "offsets": [ [ 456, 471 ] ], "normalized": [] }, { "id": "3152", "type": "protein_complex", "text": [ "MHC" ], "offsets": [ [ 464, 467 ] ], "normalized": [] }, { "id": "3153", "type": "DNA_domain_or_region", "text": [ "CIITA" ], "offsets": [ [ 501, 506 ] ], "normalized": [] }, { "id": "3154", "type": "DNA_domain_or_region", "text": [ "CIITA" ], "offsets": [ [ 534, 539 ] ], "normalized": [] }, { "id": "3155", "type": "DNA_family_or_group", "text": [ "MHC class II gene-specific transcription activator" ], "offsets": [ [ 546, 596 ] ], "normalized": [] }, { "id": "3156", "type": "protein_complex", "text": [ "MHC class II" ], "offsets": [ [ 546, 558 ] ], "normalized": [] }, { "id": "3157", "type": "other_name", "text": [ "transcription activation function" ], "offsets": [ [ 602, 635 ] ], "normalized": [] }, { "id": "3158", "type": "protein_domain_or_region", "text": [ "N-terminal acidic domain" ], "offsets": [ [ 655, 679 ] ], "normalized": [] }, { "id": "3159", "type": "protein_domain_or_region", "text": [ "amino acids 26-137" ], "offsets": [ [ 681, 699 ] ], "normalized": [] }, { "id": "3160", "type": "protein_domain_or_region", "text": [ "heterologous viral transcription-activating domain" ], "offsets": [ [ 746, 796 ] ], "normalized": [] }, { "id": "3161", "type": "protein_molecule", "text": [ "CIITA" ], "offsets": [ [ 817, 822 ] ], "normalized": [] }, { "id": "3162", "type": "DNA_domain_or_region", "text": [ "MHC class II genes" ], "offsets": [ [ 839, 857 ] ], "normalized": [] }, { "id": "3163", "type": "protein_complex", "text": [ "MHC class II" ], "offsets": [ [ 839, 851 ] ], "normalized": [] }, { "id": "3164", "type": "DNA_domain_or_region", "text": [ "DR" ], "offsets": [ [ 859, 861 ] ], "normalized": [] }, { "id": "3165", "type": "DNA_domain_or_region", "text": [ "DQ" ], "offsets": [ [ 863, 865 ] ], "normalized": [] }, { "id": "3166", "type": "DNA_domain_or_region", "text": [ "DP" ], "offsets": [ [ 870, 872 ] ], "normalized": [] }, { "id": "3167", "type": "protein_domain_or_region", "text": [ "C-terminal residues" ], "offsets": [ [ 903, 922 ] ], "normalized": [] }, { "id": "3168", "type": "protein_domain_or_region", "text": [ "amino acids 317-1130" ], "offsets": [ [ 924, 944 ] ], "normalized": [] }, { "id": "3169", "type": "DNA_domain_or_region", "text": [ "multiple cis elements" ], "offsets": [ [ 970, 991 ] ], "normalized": [] }, { "id": "3170", "type": "DNA_domain_or_region", "text": [ "S" ], "offsets": [ [ 1004, 1005 ] ], "normalized": [] }, { "id": "3171", "type": "DNA_domain_or_region", "text": [ "X2" ], "offsets": [ [ 1010, 1012 ] ], "normalized": [] }, { "id": "3172", "type": "DNA_domain_or_region", "text": [ "DR alpha proximal promoter" ], "offsets": [ [ 1021, 1047 ] ], "normalized": [] }, { "id": "3173", "type": "DNA_domain_or_region", "text": [ "proximal promoter" ], "offsets": [ [ 1030, 1047 ] ], "normalized": [] }, { "id": "3174", "type": "cell_line", "text": [ "group II CID cells" ], "offsets": [ [ 1051, 1069 ] ], "normalized": [] }, { "id": "3175", "type": "protein_molecule", "text": [ "CIITA" ], "offsets": [ [ 1073, 1078 ] ], "normalized": [] }, { "id": "3176", "type": "other_name", "text": [ "CIITA overexpression" ], "offsets": [ [ 1096, 1116 ] ], "normalized": [] }, { "id": "3177", "type": "protein_molecule", "text": [ "CIITA" ], "offsets": [ [ 1096, 1101 ] ], "normalized": [] }, { "id": "3178", "type": "cell_type", "text": [ "normal cells" ], "offsets": [ [ 1120, 1132 ] ], "normalized": [] }, { "id": "3179", "type": "other_name", "text": [ "class II expression" ], "offsets": [ [ 1150, 1169 ] ], "normalized": [] }, { "id": "3180", "type": "other_name", "text": [ "CIITA expression" ], "offsets": [ [ 1201, 1217 ] ], "normalized": [] }, { "id": "3181", "type": "protein_molecule", "text": [ "CIITA" ], "offsets": [ [ 1201, 1206 ] ], "normalized": [] }, { "id": "3182", "type": "other_name", "text": [ "downstream interactor" ], "offsets": [ [ 1269, 1290 ] ], "normalized": [] }, { "id": "3183", "type": "other_name", "text": [ "transcription" ], "offsets": [ [ 1301, 1314 ] ], "normalized": [] } ]

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[ { "id": "3185", "type": "title", "text": [ "Monocyte tethering by P-selectin regulates monocyte chemotactic protein-1 and tumor necrosis factor-alpha secretion. Signal integration and NF-kappa B translocation [see comments]" ], "offsets": [ [ 0, 179 ] ] }, { "id": "3186", "type": "abstract", "text": [ "Adhesion molecules that tether circulating leukocytes to endothelial cells may also transduce or modulate outside-in signals for cellular activation, providing an initial regulatory point in the inflammatory response. Adhesion of human monocytes to P-selectin, the most rapidly expressed endothelial tethering factor, increased the secretion of monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) by the leukocytes when they were stimulated with platelet-activating factor. Increased cytokine secretion was specifically inhibited by G1, an anti-P-selectin mAb that prevents P-selectin from binding to its ligand (P-selectin glycoprotein ligand-1) on myeloid cells. Moreover, tethering by P-selectin specifically enhanced nuclear translocation of nuclear factor-kappa B (NF-kappa B), a transcription factor required for expression of MCP-1, TNF-alpha, and other immediate-early genes. These results demonstrate that P-selectin, through its ligands on monocytes, may locally regulate cytokine secretion in inflamed tissues." ], "offsets": [ [ 180, 1232 ] ] } ]

[ { "id": "3187", "type": "protein_molecule", "text": [ "P-selectin" ], "offsets": [ [ 22, 32 ] ], "normalized": [] }, { "id": "3188", "type": "protein_molecule", "text": [ "monocyte chemotactic protein-1" ], "offsets": [ [ 43, 73 ] ], "normalized": [] }, { "id": "3189", "type": "other_name", "text": [ "tumor necrosis factor-alpha secretion" ], "offsets": [ [ 78, 115 ] ], "normalized": [] }, { "id": "3190", "type": "protein_molecule", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 78, 105 ] ], "normalized": [] }, { "id": "3191", "type": "other_name", "text": [ "Signal integration" ], "offsets": [ [ 117, 135 ] ], "normalized": [] }, { "id": "3192", "type": "other_name", "text": [ "NF-kappa B translocation" ], "offsets": [ [ 140, 164 ] ], "normalized": [] }, { "id": "3193", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 140, 150 ] ], "normalized": [] }, { "id": "3194", "type": "protein_family_or_group", "text": [ "Adhesion molecules" ], "offsets": [ [ 180, 198 ] ], "normalized": [] }, { "id": "3195", "type": "cell_type", "text": [ "circulating leukocytes" ], "offsets": [ [ 211, 233 ] ], "normalized": [] }, { "id": "3196", "type": "cell_type", "text": [ "endothelial cells" ], "offsets": [ [ 237, 254 ] ], "normalized": [] }, { "id": "3197", "type": "other_name", "text": [ "cellular activation" ], "offsets": [ [ 309, 328 ] ], "normalized": [] }, { "id": "3198", "type": "other_name", "text": [ "inflammatory response" ], "offsets": [ [ 375, 396 ] ], "normalized": [] }, { "id": "3199", "type": "cell_type", "text": [ "human monocytes" ], "offsets": [ [ 410, 425 ] ], "normalized": [] }, { "id": "3200", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 416, 425 ] ], "normalized": [] }, { "id": "3201", "type": "protein_molecule", "text": [ "P-selectin" ], "offsets": [ [ 429, 439 ] ], "normalized": [] }, { "id": "3202", "type": "protein_molecule", "text": [ "endothelial tethering factor" ], "offsets": [ [ 468, 496 ] ], "normalized": [] }, { "id": "3203", "type": "protein_molecule", "text": [ "monocyte chemotactic protein-1" ], "offsets": [ [ 525, 555 ] ], "normalized": [] }, { "id": "3204", "type": "protein_molecule", "text": [ "MCP-1" ], "offsets": [ [ 557, 562 ] ], "normalized": [] }, { "id": "3205", "type": "protein_molecule", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 568, 595 ] ], "normalized": [] }, { "id": "3206", "type": "protein_molecule", "text": [ "TNF-alpha" ], "offsets": [ [ 597, 606 ] ], "normalized": [] }, { "id": "3207", "type": "cell_type", "text": [ "leukocytes" ], "offsets": [ [ 615, 625 ] ], "normalized": [] }, { "id": "3208", "type": "protein_molecule", "text": [ "platelet-activating factor" ], "offsets": [ [ 657, 683 ] ], "normalized": [] }, { "id": "3209", "type": "protein_molecule", "text": [ "G1" ], "offsets": [ [ 744, 746 ] ], "normalized": [] }, { "id": "3210", "type": "protein_family_or_group", "text": [ "anti-P-selectin mAb" ], "offsets": [ [ 751, 770 ] ], "normalized": [] }, { "id": "3211", "type": "protein_molecule", "text": [ "P-selectin" ], "offsets": [ [ 756, 766 ] ], "normalized": [] }, { "id": "3212", "type": "protein_molecule", "text": [ "P-selectin" ], "offsets": [ [ 785, 795 ] ], "normalized": [] }, { "id": "3213", "type": "protein_molecule", "text": [ "P-selectin glycoprotein ligand-1" ], "offsets": [ [ 824, 856 ] ], "normalized": [] }, { "id": "3214", "type": "protein_molecule", "text": [ "P-selectin" ], "offsets": [ [ 824, 834 ] ], "normalized": [] }, { "id": "3215", "type": "cell_type", "text": [ "myeloid cells" ], "offsets": [ [ 861, 874 ] ], "normalized": [] }, { "id": "3216", "type": "protein_molecule", "text": [ "P-selectin" ], "offsets": [ [ 899, 909 ] ], "normalized": [] }, { "id": "3217", "type": "other_name", "text": [ "nuclear translocation" ], "offsets": [ [ 932, 953 ] ], "normalized": [] }, { "id": "3218", "type": "protein_molecule", "text": [ "nuclear factor-kappa B" ], "offsets": [ [ 957, 979 ] ], "normalized": [] }, { "id": "3219", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 981, 991 ] ], "normalized": [] }, { "id": "3220", "type": "protein_family_or_group", "text": [ "transcription factor" ], "offsets": [ [ 996, 1016 ] ], "normalized": [] }, { "id": "3221", "type": "protein_molecule", "text": [ "MCP-1" ], "offsets": [ [ 1044, 1049 ] ], "normalized": [] }, { "id": "3222", "type": "protein_molecule", "text": [ "TNF-alpha" ], "offsets": [ [ 1051, 1060 ] ], "normalized": [] }, { "id": "3223", "type": "DNA_family_or_group", "text": [ "immediate-early genes" ], "offsets": [ [ 1072, 1093 ] ], "normalized": [] }, { "id": "3224", "type": "protein_molecule", "text": [ "P-selectin" ], "offsets": [ [ 1126, 1136 ] ], "normalized": [] }, { "id": "3225", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 1161, 1170 ] ], "normalized": [] }, { "id": "3226", "type": "other_name", "text": [ "cytokine secretion" ], "offsets": [ [ 1193, 1211 ] ], "normalized": [] }, { "id": "3227", "type": "protein_family_or_group", "text": [ "cytokine" ], "offsets": [ [ 1193, 1201 ] ], "normalized": [] }, { "id": "3228", "type": "tissue", "text": [ "inflamed tissues" ], "offsets": [ [ 1215, 1231 ] ], "normalized": [] } ]

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[ { "id": "3230", "type": "title", "text": [ "Functional roles of in vivo footprinted DNA motifs within an alpha-globin enhancer. Erythroid lineage and developmental stage specificities." ], "offsets": [ [ 0, 140 ] ] }, { "id": "3231", "type": "abstract", "text": [ "Transcriptional regulation of the human alpha-like globin genes, embryonic zeta 2 and adult alpha, during erythroid development is mediated by a distal enhancer, HS-40. Previous protein-DNA binding studies have shown that HS-40 consists of multiple nuclear factor binding motifs that are occupied in vivo in an erythroid lineage- and developmental stage-specific manner. We have systematically analyzed the functional roles of these factor binding motifs of HS-40 by site-directed mutagenesis and transient expression assay in erythroid cell cultures. Three of these HS-40 enhancer motifs, 5'NF-E2/AP1, GT II, and GATA-1(c), positively regulate the zeta 2-globin promoter activity in embryonic/fetal erythroid K562 cells and the adult alpha-globin promoter activity in adult erythroid MEL cells. On the other hand, the 3'NF-E2/AP1 motif is able to exert both positive and negative regulatory effects on the zeta 2-globin promoter activity in K562 cells, and this dual function appears to be modulated through differential binding of the ubiquitous AP1 factors and the erythroid-enriched NF-E2 factor. Mutation in the GATA-1(d) motif, which exhibits an adult erythroid-specific genomic footprint, decreases the HS-40 enhancer function in dimethyl sulfoxide-induced MEL cells but not in K562 cells. These studies have defined the regulatory roles of the different HS-40 motifs. The remarkable correlation between genomic footprinting data and the mutagenesis results also suggests that the erythroid lineage- and developmental stage-specific regulation of human alpha-like globin promoters is indeed modulated by stable binding of specific nuclear factors in vivo." ], "offsets": [ [ 141, 1803 ] ] } ]

[ { "id": "3232", "type": "DNA_family_or_group", "text": [ "in vivo footprinted DNA motifs" ], "offsets": [ [ 20, 50 ] ], "normalized": [] }, { "id": "3233", "type": "DNA_domain_or_region", "text": [ "alpha-globin enhancer" ], "offsets": [ [ 61, 82 ] ], "normalized": [] }, { "id": "3234", "type": "other_name", "text": [ "Erythroid lineage" ], "offsets": [ [ 84, 101 ] ], "normalized": [] }, { "id": "3235", "type": "other_name", "text": [ "Transcriptional regulation" ], "offsets": [ [ 141, 167 ] ], "normalized": [] }, { "id": "3236", "type": "DNA_family_or_group", "text": [ "human alpha-like globin genes" ], "offsets": [ [ 175, 204 ] ], "normalized": [] }, { "id": "3237", "type": "DNA_domain_or_region", "text": [ "embryonic zeta 2" ], "offsets": [ [ 206, 222 ] ], "normalized": [] }, { "id": "3238", "type": "DNA_domain_or_region", "text": [ "adult alpha" ], "offsets": [ [ 227, 238 ] ], "normalized": [] }, { "id": "3239", "type": "other_name", "text": [ "erythroid development" ], "offsets": [ [ 247, 268 ] ], "normalized": [] }, { "id": "3240", "type": "DNA_domain_or_region", "text": [ "distal enhancer" ], "offsets": [ [ 286, 301 ] ], "normalized": [] }, { "id": "3241", "type": "DNA_domain_or_region", "text": [ "HS-40" ], "offsets": [ [ 303, 308 ] ], "normalized": [] }, { "id": "3242", "type": "other_name", "text": [ "protein-DNA binding studies" ], "offsets": [ [ 319, 346 ] ], "normalized": [] }, { "id": "3243", "type": "DNA_domain_or_region", "text": [ "HS-40" ], "offsets": [ [ 363, 368 ] ], "normalized": [] }, { "id": "3244", "type": "DNA_family_or_group", "text": [ "nuclear factor binding motifs" ], "offsets": [ [ 390, 419 ] ], "normalized": [] }, { "id": "3245", "type": "(AND other_name other_name)", "text": [ "erythroid lineage- and developmental stage-specific manner" ], "offsets": [ [ 452, 510 ] ], "normalized": [] }, { "id": "3246", "type": "", "text": [ "erythroid lineage-" ], "offsets": [ [ 452, 470 ] ], "normalized": [] }, { "id": "3247", "type": "", "text": [ "developmental stage-" ], "offsets": [ [ 475, 495 ] ], "normalized": [] }, { "id": "3248", "type": "", "text": [ "specific manner" ], "offsets": [ [ 495, 510 ] ], "normalized": [] }, { "id": "3249", "type": "DNA_domain_or_region", "text": [ "factor binding motifs" ], "offsets": [ [ 574, 595 ] ], "normalized": [] }, { "id": "3250", "type": "DNA_domain_or_region", "text": [ "HS-40" ], "offsets": [ [ 599, 604 ] ], "normalized": [] }, { "id": "3251", "type": "other_name", "text": [ "site-directed mutagenesis" ], "offsets": [ [ 608, 633 ] ], "normalized": [] }, { "id": "3252", "type": "other_name", "text": [ "transient expression assay" ], "offsets": [ [ 638, 664 ] ], "normalized": [] }, { "id": "3253", "type": "cell_line", "text": [ "erythroid cell cultures" ], "offsets": [ [ 668, 691 ] ], "normalized": [] }, { "id": "3254", "type": "DNA_domain_or_region", "text": [ "HS-40 enhancer motifs" ], "offsets": [ [ 708, 729 ] ], "normalized": [] }, { "id": "3255", "type": "DNA_domain_or_region", "text": [ "HS-40" ], "offsets": [ [ 708, 713 ] ], "normalized": [] }, { "id": "3256", "type": "DNA_domain_or_region", "text": [ "5'NF-E2/AP1" ], "offsets": [ [ 731, 742 ] ], "normalized": [] }, { "id": "3257", "type": "DNA_domain_or_region", "text": [ "GT II" ], "offsets": [ [ 744, 749 ] ], "normalized": [] }, { "id": "3258", "type": "DNA_domain_or_region", "text": [ "GATA-1(c)" ], "offsets": [ [ 755, 764 ] ], "normalized": [] }, { "id": "3259", "type": "other_name", "text": [ "zeta 2-globin promoter activity" ], "offsets": [ [ 790, 821 ] ], "normalized": [] }, { "id": "3260", "type": "DNA_domain_or_region", "text": [ "zeta 2-globin promoter" ], "offsets": [ [ 790, 812 ] ], "normalized": [] }, { "id": "3261", "type": "cell_line", "text": [ "embryonic/fetal erythroid K562 cells" ], "offsets": [ [ 825, 861 ] ], "normalized": [] }, { "id": "3262", "type": "other_name", "text": [ "adult alpha-globin promoter activity" ], "offsets": [ [ 870, 906 ] ], "normalized": [] }, { "id": "3263", "type": "DNA_domain_or_region", "text": [ "adult alpha-globin promoter" ], "offsets": [ [ 870, 897 ] ], "normalized": [] }, { "id": "3264", "type": "DNA_domain_or_region", "text": [ "adult alpha" ], "offsets": [ [ 870, 881 ] ], "normalized": [] }, { "id": "3265", "type": "cell_line", "text": [ "adult erythroid MEL cells" ], "offsets": [ [ 910, 935 ] ], "normalized": [] }, { "id": "3266", "type": "DNA_domain_or_region", "text": [ "3'NF-E2/AP1 motif" ], "offsets": [ [ 960, 977 ] ], "normalized": [] }, { "id": "3267", "type": "other_name", "text": [ "regulatory effects" ], "offsets": [ [ 1022, 1040 ] ], "normalized": [] }, { "id": "3268", "type": "other_name", "text": [ "zeta 2-globin promoter activity" ], "offsets": [ [ 1048, 1079 ] ], "normalized": [] }, { "id": "3269", "type": "DNA_domain_or_region", "text": [ "zeta 2-globin promoter" ], "offsets": [ [ 1048, 1070 ] ], "normalized": [] }, { "id": "3270", "type": "cell_line", "text": [ "K562 cells" ], "offsets": [ [ 1083, 1093 ] ], "normalized": [] }, { "id": "3271", "type": "protein_family_or_group", "text": [ "ubiquitous AP1 factors" ], "offsets": [ [ 1178, 1200 ] ], "normalized": [] }, { "id": "3272", "type": "protein_molecule", "text": [ "erythroid-enriched NF-E2 factor" ], "offsets": [ [ 1209, 1240 ] ], "normalized": [] }, { "id": "3273", "type": "DNA_domain_or_region", "text": [ "GATA-1(d) motif" ], "offsets": [ [ 1258, 1273 ] ], "normalized": [] }, { "id": "3274", "type": "DNA_domain_or_region", "text": [ "adult erythroid-specific genomic footprint" ], "offsets": [ [ 1293, 1335 ] ], "normalized": [] }, { "id": "3275", "type": "DNA_domain_or_region", "text": [ "HS-40 enhancer" ], "offsets": [ [ 1351, 1365 ] ], "normalized": [] }, { "id": "3276", "type": "DNA_domain_or_region", "text": [ "HS-40" ], "offsets": [ [ 1351, 1356 ] ], "normalized": [] }, { "id": "3277", "type": "cell_line", "text": [ "dimethyl sulfoxide-induced MEL cells" ], "offsets": [ [ 1378, 1414 ] ], "normalized": [] }, { "id": "3278", "type": "cell_line", "text": [ "K562 cells" ], "offsets": [ [ 1426, 1436 ] ], "normalized": [] }, { "id": "3279", "type": "DNA_domain_or_region", "text": [ "HS-40 motifs" ], "offsets": [ [ 1503, 1515 ] ], "normalized": [] }, { "id": "3280", "type": "DNA_domain_or_region", "text": [ "HS-40" ], "offsets": [ [ 1503, 1508 ] ], "normalized": [] }, { "id": "3281", "type": "other_name", "text": [ "genomic footprinting data" ], "offsets": [ [ 1552, 1577 ] ], "normalized": [] }, { "id": "3282", "type": "other_name", "text": [ "mutagenesis results" ], "offsets": [ [ 1586, 1605 ] ], "normalized": [] }, { "id": "3283", "type": "(AND other_name other_name)", "text": [ "erythroid lineage- and developmental stage-specific regulation" ], "offsets": [ [ 1629, 1691 ] ], "normalized": [] }, { "id": "3284", "type": "", "text": [ "erythroid lineage-" ], "offsets": [ [ 1629, 1647 ] ], "normalized": [] }, { "id": "3285", "type": "", "text": [ "developmental stage-" ], "offsets": [ [ 1652, 1672 ] ], "normalized": [] }, { "id": "3286", "type": "", "text": [ "specific regulation" ], "offsets": [ [ 1672, 1691 ] ], "normalized": [] }, { "id": "3287", "type": "DNA_domain_or_region", "text": [ "human alpha-like globin promoters" ], "offsets": [ [ 1695, 1728 ] ], "normalized": [] }, { "id": "3288", "type": "protein_family_or_group", "text": [ "specific nuclear factors" ], "offsets": [ [ 1770, 1794 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "3290", "type": "title", "text": [ "Nitric oxide-stimulated guanine nucleotide exchange on p21ras." ], "offsets": [ [ 0, 62 ] ] }, { "id": "3291", "type": "abstract", "text": [ "The protooncogene p21ras, a monomeric G protein family member, plays a critical role in converting extracellular signals into intracellular biochemical events. Here, we report that nitric oxide (NO) activates p21ras in human T cells as evidenced by an increase in GTP-bound p21ras. In vitro studies using pure recombinant p21ras demonstrate that the activation is direct and reversible. Circular dichroism analysis reveals that NO induces a profound conformational change in p21ras in association with GDP/GTP exchange. The mechanism of activation is due to S-nitrosylation of a critical cysteine residue which stimulates guanine nucleotide exchange. Furthermore, we demonstrate that p21ras is essential for NO-induced downstream signaling, such as NF-kappa B activation, and that endogenous NO can activate p21ras in the same cell. These studies identify p21ras as a target of the same cell. These studies identify p21ras as a target of NO in T cells and suggest that NO activates p21ras by an action which mimics that of guanine nucleotide exchange factors." ], "offsets": [ [ 63, 1122 ] ] } ]

[ { "id": "3292", "type": "other_name", "text": [ "Nitric oxide-stimulated guanine nucleotide exchange" ], "offsets": [ [ 0, 51 ] ], "normalized": [] }, { "id": "3293", "type": "inorganic", "text": [ "Nitric oxide" ], "offsets": [ [ 0, 12 ] ], "normalized": [] }, { "id": "3294", "type": "nucleotide", "text": [ "guanine nucleotide" ], "offsets": [ [ 24, 42 ] ], "normalized": [] }, { "id": "3295", "type": "protein_molecule", "text": [ "p21ras" ], "offsets": [ [ 55, 61 ] ], "normalized": [] }, { "id": "3296", "type": "DNA_domain_or_region", "text": [ "protooncogene p21ras" ], "offsets": [ [ 67, 87 ] ], "normalized": [] }, { "id": "3297", "type": "protein_family_or_group", "text": [ "monomeric G protein family member" ], "offsets": [ [ 91, 124 ] ], "normalized": [] }, { "id": "3298", "type": "other_name", "text": [ "converting extracellular signals" ], "offsets": [ [ 151, 183 ] ], "normalized": [] }, { "id": "3299", "type": "other_name", "text": [ "intracellular biochemical events" ], "offsets": [ [ 189, 221 ] ], "normalized": [] }, { "id": "3300", "type": "inorganic", "text": [ "nitric oxide" ], "offsets": [ [ 244, 256 ] ], "normalized": [] }, { "id": "3301", "type": "inorganic", "text": [ "NO" ], "offsets": [ [ 258, 260 ] ], "normalized": [] }, { "id": "3302", "type": "DNA_domain_or_region", "text": [ "p21ras" ], "offsets": [ [ 272, 278 ] ], "normalized": [] }, { "id": "3303", "type": "cell_type", "text": [ "human T cells" ], "offsets": [ [ 282, 295 ] ], "normalized": [] }, { "id": "3304", "type": "multi_cell", "text": [ "human" ], "offsets": [ [ 282, 287 ] ], "normalized": [] }, { "id": "3305", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 288, 295 ] ], "normalized": [] }, { "id": "3306", "type": "protein_molecule", "text": [ "GTP-bound p21ras" ], "offsets": [ [ 327, 343 ] ], "normalized": [] }, { "id": "3307", "type": "nucleotide", "text": [ "GTP" ], "offsets": [ [ 327, 330 ] ], "normalized": [] }, { "id": "3308", "type": "protein_molecule", "text": [ "pure recombinant p21ras" ], "offsets": [ [ 368, 391 ] ], "normalized": [] }, { "id": "3309", "type": "inorganic", "text": [ "NO" ], "offsets": [ [ 491, 493 ] ], "normalized": [] }, { "id": "3310", "type": "other_name", "text": [ "profound conformational change" ], "offsets": [ [ 504, 534 ] ], "normalized": [] }, { "id": "3311", "type": "DNA_domain_or_region", "text": [ "p21ras" ], "offsets": [ [ 538, 544 ] ], "normalized": [] }, { "id": "3312", "type": "other_name", "text": [ "GDP/GTP exchange" ], "offsets": [ [ 565, 581 ] ], "normalized": [] }, { "id": "3313", "type": "nucleotide", "text": [ "GDP" ], "offsets": [ [ 565, 568 ] ], "normalized": [] }, { "id": "3314", "type": "nucleotide", "text": [ "/GTP" ], "offsets": [ [ 568, 572 ] ], "normalized": [] }, { "id": "3315", "type": "other_name", "text": [ "mechanism of activation" ], "offsets": [ [ 587, 610 ] ], "normalized": [] }, { "id": "3316", "type": "other_name", "text": [ "S-nitrosylation" ], "offsets": [ [ 621, 636 ] ], "normalized": [] }, { "id": "3317", "type": "amino_acid_monomer", "text": [ "cysteine residue" ], "offsets": [ [ 651, 667 ] ], "normalized": [] }, { "id": "3318", "type": "protein_molecule", "text": [ "p21ras" ], "offsets": [ [ 747, 753 ] ], "normalized": [] }, { "id": "3319", "type": "other_name", "text": [ "NO-induced downstream signaling" ], "offsets": [ [ 771, 802 ] ], "normalized": [] }, { "id": "3320", "type": "inorganic", "text": [ "NO" ], "offsets": [ [ 771, 773 ] ], "normalized": [] }, { "id": "3321", "type": "other_name", "text": [ "NF-kappa B activation" ], "offsets": [ [ 812, 833 ] ], "normalized": [] }, { "id": "3322", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 812, 822 ] ], "normalized": [] }, { "id": "3323", "type": "inorganic", "text": [ "endogenous NO" ], "offsets": [ [ 844, 857 ] ], "normalized": [] }, { "id": "3324", "type": "inorganic", "text": [ "NO" ], "offsets": [ [ 855, 857 ] ], "normalized": [] }, { "id": "3325", "type": "protein_molecule", "text": [ "p21ras" ], "offsets": [ [ 871, 877 ] ], "normalized": [] }, { "id": "3326", "type": "DNA_domain_or_region", "text": [ "p21ras" ], "offsets": [ [ 919, 925 ] ], "normalized": [] }, { "id": "3327", "type": "protein_molecule", "text": [ "p21ras" ], "offsets": [ [ 919, 925 ] ], "normalized": [] }, { "id": "3328", "type": "DNA_domain_or_region", "text": [ "p21ras" ], "offsets": [ [ 979, 985 ] ], "normalized": [] }, { "id": "3329", "type": "protein_molecule", "text": [ "p21ras" ], "offsets": [ [ 979, 985 ] ], "normalized": [] }, { "id": "3330", "type": "inorganic", "text": [ "NO" ], "offsets": [ [ 1001, 1003 ] ], "normalized": [] }, { "id": "3331", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 1007, 1014 ] ], "normalized": [] }, { "id": "3332", "type": "inorganic", "text": [ "NO" ], "offsets": [ [ 1032, 1034 ] ], "normalized": [] }, { "id": "3333", "type": "DNA_domain_or_region", "text": [ "p21ras" ], "offsets": [ [ 1045, 1051 ] ], "normalized": [] }, { "id": "3334", "type": "protein_molecule", "text": [ "p21ras" ], "offsets": [ [ 1045, 1051 ] ], "normalized": [] }, { "id": "3335", "type": "protein_family_or_group", "text": [ "guanine nucleotide exchange factors" ], "offsets": [ [ 1086, 1121 ] ], "normalized": [] }, { "id": "3336", "type": "nucleotide", "text": [ "guanine" ], "offsets": [ [ 1086, 1093 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "3338", "type": "title", "text": [ "Interleukin-2 promoter activity in Epstein-Barr virus-transformed B lymphocytes is controlled by nuclear factor-chi B." ], "offsets": [ [ 0, 118 ] ] }, { "id": "3339", "type": "abstract", "text": [ "The regulation of interleukin (IL)-2 gene expression has been investigated mainly in T lymphocytes, the predominant producers of IL-2. However, B cells can also synthesize IL-2. In the present study we analyzed the control of IL-2 promoter activity in Epstein-Barr virus (EBV)-transformed B cell clones which are capable of secreting IL-2 at a low level after stimulation with phorbol 12-myristate 13-acetate and the Ca2+ ionophore ionomycin. Transient transfections using reporter constructs with multiples of transcription factor binding sites from the IL-2 promoter [distal nuclear factor (NF)-AT, proximal NF-AT, AP-1/Octamer (UPS) or NF-chi B (TCEd) sites] were performed. In EBV-transformed B clones, the chi B site exerted the strongest inducible activity; the NF-AT binding sites showed either no or only weak activity compared to Jurkat T cells. An IL-2 promoter bearing a defective NF-chi B site was completely inactive in EBV-transformed B cells, while it still had activity in Jurkat T cells. In seven EBV-B cell clones or lines differing in their capacity to secrete IL-2, the activity of the IL-2 promoter correlated well with the status of IL-2 secretion. Similarly, a human immunodeficiency virus promoter, whose activity is controlled through chi B factors, was found to be active in the IL-2 producing EBV-B cells, but inactive in the non-IL-2-producing cells. Electrophoretic mobility shift assays using protein extracts from EBV-B cells and the IL-2 NF-chi B probe revealed the constitutive generation of chi B complexes in IL-2-secreting cells consisting mainly of heterodimeric p50/p65 complexes. A weaker chi B complex formation and faster-migrating complexes were detected in non-IL-2-secreting cells. These results demonstrate that the IL-2 NF-chi B site is indispensable for the activity of the IL-2 promoter in EBV-transformed B cells, whereas other transcription factors appear to be less important for IL-2 expression in these cells." ], "offsets": [ [ 119, 2081 ] ] } ]

[ { "id": "3340", "type": "other_name", "text": [ "Interleukin-2 promoter activity" ], "offsets": [ [ 0, 31 ] ], "normalized": [] }, { "id": "3341", "type": "DNA_domain_or_region", "text": [ "Interleukin-2 promoter" ], "offsets": [ [ 0, 22 ] ], "normalized": [] }, { "id": "3342", "type": "cell_line", "text": [ "Epstein-Barr virus-transformed B lymphocytes" ], "offsets": [ [ 35, 79 ] ], "normalized": [] }, { "id": "3343", "type": "virus", "text": [ "Epstein-Barr virus" ], "offsets": [ [ 35, 53 ] ], "normalized": [] }, { "id": "3344", "type": "protein_molecule", "text": [ "nuclear factor-chi B" ], "offsets": [ [ 97, 117 ] ], "normalized": [] }, { "id": "3345", "type": "other_name", "text": [ "interleukin (IL)-2 gene expression" ], "offsets": [ [ 137, 171 ] ], "normalized": [] }, { "id": "3346", "type": "DNA_domain_or_region", "text": [ "interleukin (IL)-2 gene" ], "offsets": [ [ 137, 160 ] ], "normalized": [] }, { "id": "3347", "type": "cell_type", "text": [ "T lymphocytes" ], "offsets": [ [ 204, 217 ] ], "normalized": [] }, { "id": "3348", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 248, 252 ] ], "normalized": [] }, { "id": "3349", "type": "cell_type", "text": [ "B cells" ], "offsets": [ [ 263, 270 ] ], "normalized": [] }, { "id": "3350", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 291, 295 ] ], "normalized": [] }, { "id": "3351", "type": "other_name", "text": [ "IL-2 promoter activity" ], "offsets": [ [ 345, 367 ] ], "normalized": [] }, { "id": "3352", "type": "DNA_domain_or_region", "text": [ "IL-2 promoter" ], "offsets": [ [ 345, 358 ] ], "normalized": [] }, { "id": "3353", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 345, 349 ] ], "normalized": [] }, { "id": "3354", "type": "cell_line", "text": [ "Epstein-Barr virus (EBV)-transformed B cell clones" ], "offsets": [ [ 371, 421 ] ], "normalized": [] }, { "id": "3355", "type": "virus", "text": [ "Epstein-Barr virus" ], "offsets": [ [ 371, 389 ] ], "normalized": [] }, { "id": "3356", "type": "virus", "text": [ "EBV" ], "offsets": [ [ 391, 394 ] ], "normalized": [] }, { "id": "3357", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 453, 457 ] ], "normalized": [] }, { "id": "3358", "type": "other_organic_compound", "text": [ "phorbol 12-myristate 13-acetate" ], "offsets": [ [ 496, 527 ] ], "normalized": [] }, { "id": "3359", "type": "other_organic_compound", "text": [ "Ca2+ ionophore" ], "offsets": [ [ 536, 550 ] ], "normalized": [] }, { "id": "3360", "type": "other_organic_compound", "text": [ "ionomycin" ], "offsets": [ [ 551, 560 ] ], "normalized": [] }, { "id": "3361", "type": "other_name", "text": [ "Transient transfections" ], "offsets": [ [ 562, 585 ] ], "normalized": [] }, { "id": "3362", "type": "DNA_family_or_group", "text": [ "reporter constructs" ], "offsets": [ [ 592, 611 ] ], "normalized": [] }, { "id": "3363", "type": "DNA_domain_or_region", "text": [ "transcription factor binding sites" ], "offsets": [ [ 630, 664 ] ], "normalized": [] }, { "id": "3364", "type": "DNA_domain_or_region", "text": [ "IL-2 promoter" ], "offsets": [ [ 674, 687 ] ], "normalized": [] }, { "id": "3365", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 674, 678 ] ], "normalized": [] }, { "id": "3366", "type": "protein_molecule", "text": [ "distal nuclear factor (NF)-AT" ], "offsets": [ [ 689, 718 ] ], "normalized": [] }, { "id": "3367", "type": "protein_molecule", "text": [ "proximal NF-AT" ], "offsets": [ [ 720, 734 ] ], "normalized": [] }, { "id": "3368", "type": "protein_molecule", "text": [ "AP-1/Octamer" ], "offsets": [ [ 736, 748 ] ], "normalized": [] }, { "id": "3369", "type": "protein_molecule", "text": [ "UPS" ], "offsets": [ [ 750, 753 ] ], "normalized": [] }, { "id": "3370", "type": "protein_molecule", "text": [ "NF-chi B" ], "offsets": [ [ 758, 766 ] ], "normalized": [] }, { "id": "3371", "type": "protein_molecule", "text": [ "TCEd" ], "offsets": [ [ 768, 772 ] ], "normalized": [] }, { "id": "3372", "type": "cell_line", "text": [ "EBV-transformed B clones" ], "offsets": [ [ 800, 824 ] ], "normalized": [] }, { "id": "3373", "type": "DNA_domain_or_region", "text": [ "chi B site" ], "offsets": [ [ 830, 840 ] ], "normalized": [] }, { "id": "3374", "type": "other_name", "text": [ "strongest inducible activity" ], "offsets": [ [ 853, 881 ] ], "normalized": [] }, { "id": "3375", "type": "DNA_domain_or_region", "text": [ "NF-AT binding sites" ], "offsets": [ [ 887, 906 ] ], "normalized": [] }, { "id": "3376", "type": "cell_line", "text": [ "Jurkat T cells" ], "offsets": [ [ 958, 972 ] ], "normalized": [] }, { "id": "3377", "type": "DNA_domain_or_region", "text": [ "IL-2 promoter" ], "offsets": [ [ 977, 990 ] ], "normalized": [] }, { "id": "3378", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 977, 981 ] ], "normalized": [] }, { "id": "3379", "type": "DNA_domain_or_region", "text": [ "NF-chi B site" ], "offsets": [ [ 1011, 1024 ] ], "normalized": [] }, { "id": "3380", "type": "protein_molecule", "text": [ "NF-chi B" ], "offsets": [ [ 1011, 1019 ] ], "normalized": [] }, { "id": "3381", "type": "DNA_domain_or_region", "text": [ "chi B" ], "offsets": [ [ 1014, 1019 ] ], "normalized": [] }, { "id": "3382", "type": "cell_line", "text": [ "EBV-transformed B cells" ], "offsets": [ [ 1052, 1075 ] ], "normalized": [] }, { "id": "3383", "type": "cell_type", "text": [ "B cells" ], "offsets": [ [ 1068, 1075 ] ], "normalized": [] }, { "id": "3384", "type": "cell_line", "text": [ "Jurkat T cells" ], "offsets": [ [ 1108, 1122 ] ], "normalized": [] }, { "id": "3385", "type": "cell_line", "text": [ "EBV-B cell clones" ], "offsets": [ [ 1133, 1150 ] ], "normalized": [] }, { "id": "3386", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 1199, 1203 ] ], "normalized": [] }, { "id": "3387", "type": "DNA_domain_or_region", "text": [ "IL-2 promoter" ], "offsets": [ [ 1225, 1238 ] ], "normalized": [] }, { "id": "3388", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 1225, 1229 ] ], "normalized": [] }, { "id": "3389", "type": "other_name", "text": [ "IL-2 secretion" ], "offsets": [ [ 1274, 1288 ] ], "normalized": [] }, { "id": "3390", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 1274, 1278 ] ], "normalized": [] }, { "id": "3391", "type": "DNA_domain_or_region", "text": [ "human immunodeficiency virus promoter" ], "offsets": [ [ 1303, 1340 ] ], "normalized": [] }, { "id": "3392", "type": "protein_family_or_group", "text": [ "chi B factors" ], "offsets": [ [ 1379, 1392 ] ], "normalized": [] }, { "id": "3393", "type": "cell_line", "text": [ "IL-2 producing EBV-B cells" ], "offsets": [ [ 1424, 1450 ] ], "normalized": [] }, { "id": "3394", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 1424, 1428 ] ], "normalized": [] }, { "id": "3395", "type": "cell_type", "text": [ "B cells" ], "offsets": [ [ 1443, 1450 ] ], "normalized": [] }, { "id": "3396", "type": "cell_line", "text": [ "non-IL-2-producing cells" ], "offsets": [ [ 1472, 1496 ] ], "normalized": [] }, { "id": "3397", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 1476, 1480 ] ], "normalized": [] }, { "id": "3398", "type": "other_name", "text": [ "Electrophoretic mobility shift assays" ], "offsets": [ [ 1498, 1535 ] ], "normalized": [] }, { "id": "3399", "type": "protein_N/A", "text": [ "protein extracts" ], "offsets": [ [ 1542, 1558 ] ], "normalized": [] }, { "id": "3400", "type": "cell_line", "text": [ "EBV-B cells" ], "offsets": [ [ 1564, 1575 ] ], "normalized": [] }, { "id": "3401", "type": "cell_type", "text": [ "B cells" ], "offsets": [ [ 1568, 1575 ] ], "normalized": [] }, { "id": "3402", "type": "other_name", "text": [ "IL-2 NF-chi B probe" ], "offsets": [ [ 1584, 1603 ] ], "normalized": [] }, { "id": "3403", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 1584, 1588 ] ], "normalized": [] }, { "id": "3404", "type": "protein_molecule", "text": [ "NF-chi B" ], "offsets": [ [ 1589, 1597 ] ], "normalized": [] }, { "id": "3405", "type": "protein_complex", "text": [ "chi B complexes" ], "offsets": [ [ 1644, 1659 ] ], "normalized": [] }, { "id": "3406", "type": "cell_line", "text": [ "IL-2-secreting cells" ], "offsets": [ [ 1663, 1683 ] ], "normalized": [] }, { "id": "3407", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 1663, 1667 ] ], "normalized": [] }, { "id": "3408", "type": "protein_complex", "text": [ "heterodimeric p50/p65 complexes" ], "offsets": [ [ 1705, 1736 ] ], "normalized": [] }, { "id": "3409", "type": "other_name", "text": [ "chi B complex formation" ], "offsets": [ [ 1747, 1770 ] ], "normalized": [] }, { "id": "3410", "type": "DNA_domain_or_region", "text": [ "chi B" ], "offsets": [ [ 1747, 1752 ] ], "normalized": [] }, { "id": "3411", "type": "cell_line", "text": [ "non-IL-2-secreting cells" ], "offsets": [ [ 1819, 1843 ] ], "normalized": [] }, { "id": "3412", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 1823, 1827 ] ], "normalized": [] }, { "id": "3413", "type": "DNA_domain_or_region", "text": [ "IL-2 NF-chi B site" ], "offsets": [ [ 1880, 1898 ] ], "normalized": [] }, { "id": "3414", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 1880, 1884 ] ], "normalized": [] }, { "id": "3415", "type": "protein_molecule", "text": [ "NF-chi B" ], "offsets": [ [ 1885, 1893 ] ], "normalized": [] }, { "id": "3416", "type": "DNA_domain_or_region", "text": [ "IL-2 promoter" ], "offsets": [ [ 1940, 1953 ] ], "normalized": [] }, { "id": "3417", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 1940, 1944 ] ], "normalized": [] }, { "id": "3418", "type": "cell_line", "text": [ "EBV-transformed B cells" ], "offsets": [ [ 1957, 1980 ] ], "normalized": [] }, { "id": "3419", "type": "cell_type", "text": [ "B cells" ], "offsets": [ [ 1973, 1980 ] ], "normalized": [] }, { "id": "3420", "type": "protein_family_or_group", "text": [ "transcription factors" ], "offsets": [ [ 1996, 2017 ] ], "normalized": [] }, { "id": "3421", "type": "other_name", "text": [ "IL-2 expression" ], "offsets": [ [ 2050, 2065 ] ], "normalized": [] }, { "id": "3422", "type": "protein_molecule", "text": [ "IL-2" ], "offsets": [ [ 2050, 2054 ] ], "normalized": [] } ]

[]

[]

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[ { "id": "3424", "type": "title", "text": [ "Latent membrane protein-1 induces cyclin D2 expression, pRb hyperphosphorylation, and loss of TGF-beta 1-mediated growth inhibition in EBV-positive B cells." ], "offsets": [ [ 0, 156 ] ] }, { "id": "3425", "type": "abstract", "text": [ "The normal cell cycle is regulated by several molecules, such as the tumor-suppressor protein pRb, the G1 cyclins, the cyclin-dependent kinases, and their inhibitors. These regulators are targeted by negative growth regulatory signals, such as that provided by TGF-beta. Here, we show that the presence of either wild-type EBV or its transforming latent membrane protein-1 (LMP-1) results in the loss of TGF-beta 1-mediated growth inhibition in human B cells. Chemical cross-linking with 125I-labeled TGF-beta 1 showed an essentially normal TGF-beta receptor profile in EBV-positive and EBV-negative Burkitt's lymphoma cell lines, and these receptors were shown to be functional in transducing signals, as evidenced by the TGF-beta 1-mediated modulation of junB gene expression. However, TGF-beta 1 did not induce dephosphorylation of pRb in EBV (or LMP-1)-positive cells as opposed to EBV-negative cells, suggesting a dichotomy in the TGF-beta 1 signaling pathway leading to separable gene regulatory and growth inhibitory responses. Furthermore, LMP-1 was found to induce the expression of cyclin D2; normal B cells or EBV-negative Burkitt's lymphoma cells do not express D-type cyclins. Taken together, these data point to a potential mechanism underlying EBV-mediated B cell transformation whereby constitutive induction of key cell cycle regulators by LMP-1 can lead to pRb hyperphosphorylation and uncontrolled cell proliferation." ], "offsets": [ [ 157, 1593 ] ] } ]

[ { "id": "3426", "type": "protein_molecule", "text": [ "Latent membrane protein-1" ], "offsets": [ [ 0, 25 ] ], "normalized": [] }, { "id": "3427", "type": "other_name", "text": [ "cyclin D2 expression" ], "offsets": [ [ 34, 54 ] ], "normalized": [] }, { "id": "3428", "type": "protein_molecule", "text": [ "cyclin D2" ], "offsets": [ [ 34, 43 ] ], "normalized": [] }, { "id": "3429", "type": "other_name", "text": [ "pRb hyperphosphorylation" ], "offsets": [ [ 56, 80 ] ], "normalized": [] }, { "id": "3430", "type": "protein_molecule", "text": [ "pRb" ], "offsets": [ [ 56, 59 ] ], "normalized": [] }, { "id": "3431", "type": "other_name", "text": [ "TGF-beta 1-mediated growth inhibition" ], "offsets": [ [ 94, 131 ] ], "normalized": [] }, { "id": "3432", "type": "protein_molecule", "text": [ "TGF-beta 1" ], "offsets": [ [ 94, 104 ] ], "normalized": [] }, { "id": "3433", "type": "cell_type", "text": [ "EBV-positive B cells" ], "offsets": [ [ 135, 155 ] ], "normalized": [] }, { "id": "3434", "type": "cell_type", "text": [ "B cells" ], "offsets": [ [ 148, 155 ] ], "normalized": [] }, { "id": "3435", "type": "protein_molecule", "text": [ "tumor-suppressor protein pRb" ], "offsets": [ [ 226, 254 ] ], "normalized": [] }, { "id": "3436", "type": "protein_molecule", "text": [ "pRb" ], "offsets": [ [ 251, 254 ] ], "normalized": [] }, { "id": "3437", "type": "protein_family_or_group", "text": [ "G1 cyclins" ], "offsets": [ [ 260, 270 ] ], "normalized": [] }, { "id": "3438", "type": "protein_family_or_group", "text": [ "cyclin-dependent kinases" ], "offsets": [ [ 276, 300 ] ], "normalized": [] }, { "id": "3439", "type": "other_name", "text": [ "inhibitors" ], "offsets": [ [ 312, 322 ] ], "normalized": [] }, { "id": "3440", "type": "other_name", "text": [ "regulatory signals" ], "offsets": [ [ 373, 391 ] ], "normalized": [] }, { "id": "3441", "type": "protein_molecule", "text": [ "TGF-beta" ], "offsets": [ [ 418, 426 ] ], "normalized": [] }, { "id": "3442", "type": "virus", "text": [ "wild-type EBV" ], "offsets": [ [ 470, 483 ] ], "normalized": [] }, { "id": "3443", "type": "protein_molecule", "text": [ "transforming latent membrane protein-1" ], "offsets": [ [ 491, 529 ] ], "normalized": [] }, { "id": "3444", "type": "protein_molecule", "text": [ "LMP-1" ], "offsets": [ [ 531, 536 ] ], "normalized": [] }, { "id": "3445", "type": "other_name", "text": [ "TGF-beta 1-mediated growth inhibition" ], "offsets": [ [ 561, 598 ] ], "normalized": [] }, { "id": "3446", "type": "protein_molecule", "text": [ "TGF-beta 1" ], "offsets": [ [ 561, 571 ] ], "normalized": [] }, { "id": "3447", "type": "protein_molecule", "text": [ "TGF-beta" ], "offsets": [ [ 561, 569 ] ], "normalized": [] }, { "id": "3448", "type": "cell_type", "text": [ "human B cells" ], "offsets": [ [ 602, 615 ] ], "normalized": [] }, { "id": "3449", "type": "cell_type", "text": [ "B cells" ], "offsets": [ [ 608, 615 ] ], "normalized": [] }, { "id": "3450", "type": "protein_molecule", "text": [ "125I-labeled TGF-beta 1" ], "offsets": [ [ 645, 668 ] ], "normalized": [] }, { "id": "3451", "type": "protein_molecule", "text": [ "TGF-beta 1" ], "offsets": [ [ 658, 668 ] ], "normalized": [] }, { "id": "3452", "type": "protein_molecule", "text": [ "TGF-beta" ], "offsets": [ [ 658, 666 ] ], "normalized": [] }, { "id": "3453", "type": "other_name", "text": [ "TGF-beta receptor profile" ], "offsets": [ [ 698, 723 ] ], "normalized": [] }, { "id": "3454", "type": "protein_molecule", "text": [ "TGF-beta receptor" ], "offsets": [ [ 698, 715 ] ], "normalized": [] }, { "id": "3455", "type": "(AND cell_line cell_line)", "text": [ "EBV-positive and EBV-negative Burkitt's lymphoma cell lines" ], "offsets": [ [ 727, 786 ] ], "normalized": [] }, { "id": "3456", "type": "", "text": [ "EBV-positive" ], "offsets": [ [ 727, 739 ] ], "normalized": [] }, { "id": "3457", "type": "", "text": [ "EBV-negative" ], "offsets": [ [ 744, 756 ] ], "normalized": [] }, { "id": "3458", "type": "", "text": [ "Burkitt's lymphoma cell lines" ], "offsets": [ [ 757, 786 ] ], "normalized": [] }, { "id": "3459", "type": "other_name", "text": [ "transducing signals" ], "offsets": [ [ 839, 858 ] ], "normalized": [] }, { "id": "3460", "type": "other_name", "text": [ "TGF-beta 1-mediated modulation" ], "offsets": [ [ 880, 910 ] ], "normalized": [] }, { "id": "3461", "type": "protein_molecule", "text": [ "TGF-beta 1" ], "offsets": [ [ 880, 890 ] ], "normalized": [] }, { "id": "3462", "type": "other_name", "text": [ "junB gene expression" ], "offsets": [ [ 914, 934 ] ], "normalized": [] }, { "id": "3463", "type": "DNA_family_or_group", "text": [ "junB gene" ], "offsets": [ [ 914, 923 ] ], "normalized": [] }, { "id": "3464", "type": "protein_molecule", "text": [ "TGF-beta 1" ], "offsets": [ [ 945, 955 ] ], "normalized": [] }, { "id": "3465", "type": "protein_molecule", "text": [ "pRb" ], "offsets": [ [ 992, 995 ] ], "normalized": [] }, { "id": "3466", "type": "cell_line", "text": [ "EBV (or LMP-1)-positive cells" ], "offsets": [ [ 999, 1028 ] ], "normalized": [] }, { "id": "3467", "type": "virus", "text": [ "EBV" ], "offsets": [ [ 999, 1002 ] ], "normalized": [] }, { "id": "3468", "type": "protein_molecule", "text": [ "LMP-1" ], "offsets": [ [ 1007, 1012 ] ], "normalized": [] }, { "id": "3469", "type": "cell_line", "text": [ "EBV-negative cells" ], "offsets": [ [ 1043, 1061 ] ], "normalized": [] }, { "id": "3470", "type": "virus", "text": [ "EBV" ], "offsets": [ [ 1043, 1046 ] ], "normalized": [] }, { "id": "3471", "type": "other_name", "text": [ "TGF-beta 1 signaling pathway" ], "offsets": [ [ 1093, 1121 ] ], "normalized": [] }, { "id": "3472", "type": "protein_molecule", "text": [ "TGF-beta 1" ], "offsets": [ [ 1093, 1103 ] ], "normalized": [] }, { "id": "3473", "type": "other_name", "text": [ "growth inhibitory responses" ], "offsets": [ [ 1163, 1190 ] ], "normalized": [] }, { "id": "3474", "type": "protein_molecule", "text": [ "LMP-1" ], "offsets": [ [ 1205, 1210 ] ], "normalized": [] }, { "id": "3475", "type": "protein_molecule", "text": [ "cyclin D2" ], "offsets": [ [ 1249, 1258 ] ], "normalized": [] }, { "id": "3476", "type": "cell_type", "text": [ "B cells" ], "offsets": [ [ 1267, 1274 ] ], "normalized": [] }, { "id": "3477", "type": "cell_line", "text": [ "EBV-negative Burkitt's lymphoma cells" ], "offsets": [ [ 1278, 1315 ] ], "normalized": [] }, { "id": "3478", "type": "virus", "text": [ "EBV" ], "offsets": [ [ 1278, 1281 ] ], "normalized": [] }, { "id": "3479", "type": "protein_family_or_group", "text": [ "D-type cyclins" ], "offsets": [ [ 1331, 1345 ] ], "normalized": [] }, { "id": "3480", "type": "other_name", "text": [ "EBV-mediated B cell transformation" ], "offsets": [ [ 1416, 1450 ] ], "normalized": [] }, { "id": "3481", "type": "virus", "text": [ "EBV" ], "offsets": [ [ 1416, 1419 ] ], "normalized": [] }, { "id": "3482", "type": "protein_family_or_group", "text": [ "key cell cycle regulators" ], "offsets": [ [ 1485, 1510 ] ], "normalized": [] }, { "id": "3483", "type": "protein_molecule", "text": [ "LMP-1" ], "offsets": [ [ 1514, 1519 ] ], "normalized": [] }, { "id": "3484", "type": "other_name", "text": [ "pRb hyperphosphorylation" ], "offsets": [ [ 1532, 1556 ] ], "normalized": [] }, { "id": "3485", "type": "protein_molecule", "text": [ "pRb" ], "offsets": [ [ 1532, 1535 ] ], "normalized": [] }, { "id": "3486", "type": "other_name", "text": [ "uncontrolled cell proliferation" ], "offsets": [ [ 1561, 1592 ] ], "normalized": [] } ]

[]

[]

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[ { "id": "3488", "type": "title", "text": [ "Does thyroidectomy, radioactive iodine therapy, or antithyroid drug treatment alter reactivity of patients' T cells to epitopes of thyrotropin receptor in autoimmune thyroid diseases?" ], "offsets": [ [ 0, 183 ] ] }, { "id": "3489", "type": "abstract", "text": [ "The effect of treatment on thyroid antibody production and T cell reactivity to thyroid antigens was studied in 15 patients with Graves' disease (GD) before and after thyroidectomy, 19 patients with GD before and after radioactive iodine (RAI) therapy, and 9 patients maintained euthyroid on antithyroid drugs (ATD). Twenty subjects matched for age and sex without known thyroid disease served as controls. In GD patients, the responses of peripheral blood mononuclear cells (PBMC) and TSH receptor (TSHR)-specific T cell lines to recombinant human TSHR extracellular domain, thyroglobulin, and TSHR peptides were examined on the day of surgery or RAI therapy (day 0) and also 6-8 weeks and 3-6 months thereafter. Reactivity to TSHR peptides before surgery was heterogeneous and spanned the entire extracellular domain. Six to 8 weeks after subtotal thyroidectomy, the number of patients' PBMC responding to any peptide and the average number of recognized peptides decreased. A further decrease in the T cell reactivity to TSHR peptides was observed 3-6 months after surgery. The responses of PBMC from Graves' patients before RAI therapy were less than those in the presurgical group. Six to 8 weeks after RAI therapy, the number of patients responding to any peptide and the average number of recognized peptides increased. Three to 6 months after RAI, T cell responses to TSHR peptides were less than those 6-8 weeks after RAI therapy, but still higher than the values on day 0. Responses of PBMC from patients with GD, maintained euthyroid on ATD, were lower than those before surgery or RAI therapy. The reactivity of T cell lines in different groups reflected a pattern similar to PBMC after treatment. TSHR antibody and microsomal antibody levels decreased after surgery, but increased after RAI therapy. The difference in the number of recognized peptides by patients' PBMC before RAI and surgery may reflect the effect of long term therapy with ATD in the patients before RAI vs. the shorter period in patients before surgery. The decreased T cell reactivity to thyroid antigens after thyroidectomy could be the result of removal of a major part of the thyroid gland or redistribution of suppressor-inducer T cells. The increased T cell response after RAI therapy is probably epitope specific, rather than a response to the whole TSHR molecule. Synchronous recognition of peptides 158-176 and 248-263 is important for the development of GD, and the loss of recognition of one of these epitopes may be an early sign of immune remission and a predictor of euthyroidism." ], "offsets": [ [ 184, 2761 ] ] } ]

[ { "id": "3490", "type": "other_name", "text": [ "thyroidectomy" ], "offsets": [ [ 5, 18 ] ], "normalized": [] }, { "id": "3491", "type": "other_name", "text": [ "radioactive iodine therapy" ], "offsets": [ [ 20, 46 ] ], "normalized": [] }, { "id": "3492", "type": "atom", "text": [ "iodine" ], "offsets": [ [ 32, 38 ] ], "normalized": [] }, { "id": "3493", "type": "other_name", "text": [ "antithyroid drug treatment" ], "offsets": [ [ 51, 77 ] ], "normalized": [] }, { "id": "3494", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 108, 115 ] ], "normalized": [] }, { "id": "3495", "type": "other_name", "text": [ "epitopes" ], "offsets": [ [ 119, 127 ] ], "normalized": [] }, { "id": "3496", "type": "protein_family_or_group", "text": [ "thyrotropin receptor" ], "offsets": [ [ 131, 151 ] ], "normalized": [] }, { "id": "3497", "type": "other_name", "text": [ "autoimmune thyroid diseases" ], "offsets": [ [ 155, 182 ] ], "normalized": [] }, { "id": "3498", "type": "other_name", "text": [ "thyroid antibody production" ], "offsets": [ [ 211, 238 ] ], "normalized": [] }, { "id": "3499", "type": "other_name", "text": [ "T cell reactivity" ], "offsets": [ [ 243, 260 ] ], "normalized": [] }, { "id": "3500", "type": "other_name", "text": [ "thyroid antigens" ], "offsets": [ [ 264, 280 ] ], "normalized": [] }, { "id": "3501", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 299, 307 ] ], "normalized": [] }, { "id": "3502", "type": "other_name", "text": [ "Graves' disease" ], "offsets": [ [ 313, 328 ] ], "normalized": [] }, { "id": "3503", "type": "other_name", "text": [ "GD" ], "offsets": [ [ 330, 332 ] ], "normalized": [] }, { "id": "3504", "type": "other_name", "text": [ "thyroidectomy" ], "offsets": [ [ 351, 364 ] ], "normalized": [] }, { "id": "3505", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 369, 377 ] ], "normalized": [] }, { "id": "3506", "type": "other_name", "text": [ "GD" ], "offsets": [ [ 383, 385 ] ], "normalized": [] }, { "id": "3507", "type": "atom", "text": [ "iodine" ], "offsets": [ [ 415, 421 ] ], "normalized": [] }, { "id": "3508", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 443, 451 ] ], "normalized": [] }, { "id": "3509", "type": "other_organic_compound", "text": [ "antithyroid drugs" ], "offsets": [ [ 476, 493 ] ], "normalized": [] }, { "id": "3510", "type": "other_organic_compound", "text": [ "ATD" ], "offsets": [ [ 495, 498 ] ], "normalized": [] }, { "id": "3511", "type": "other_name", "text": [ "thyroid disease" ], "offsets": [ [ 555, 570 ] ], "normalized": [] }, { "id": "3512", "type": "other_name", "text": [ "GD" ], "offsets": [ [ 594, 596 ] ], "normalized": [] }, { "id": "3513", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 597, 605 ] ], "normalized": [] }, { "id": "3514", "type": "cell_type", "text": [ "peripheral blood mononuclear cells" ], "offsets": [ [ 624, 658 ] ], "normalized": [] }, { "id": "3515", "type": "cell_type", "text": [ "PBMC" ], "offsets": [ [ 660, 664 ] ], "normalized": [] }, { "id": "3516", "type": "cell_line", "text": [ "TSH receptor (TSHR)-specific T cell lines" ], "offsets": [ [ 670, 711 ] ], "normalized": [] }, { "id": "3517", "type": "protein_family_or_group", "text": [ "TSH receptor" ], "offsets": [ [ 670, 682 ] ], "normalized": [] }, { "id": "3518", "type": "protein_family_or_group", "text": [ "TSHR" ], "offsets": [ [ 684, 688 ] ], "normalized": [] }, { "id": "3519", "type": "protein_domain_or_region", "text": [ "recombinant human TSHR extracellular domain" ], "offsets": [ [ 715, 758 ] ], "normalized": [] }, { "id": "3520", "type": "protein_family_or_group", "text": [ "TSHR" ], "offsets": [ [ 733, 737 ] ], "normalized": [] }, { "id": "3521", "type": "protein_molecule", "text": [ "thyroglobulin" ], "offsets": [ [ 760, 773 ] ], "normalized": [] }, { "id": "3522", "type": "peptide", "text": [ "TSHR peptides" ], "offsets": [ [ 779, 792 ] ], "normalized": [] }, { "id": "3523", "type": "protein_family_or_group", "text": [ "TSHR" ], "offsets": [ [ 779, 783 ] ], "normalized": [] }, { "id": "3524", "type": "other_name", "text": [ "surgery" ], "offsets": [ [ 821, 828 ] ], "normalized": [] }, { "id": "3525", "type": "other_name", "text": [ "RAI therapy" ], "offsets": [ [ 832, 843 ] ], "normalized": [] }, { "id": "3526", "type": "peptide", "text": [ "TSHR peptides" ], "offsets": [ [ 912, 925 ] ], "normalized": [] }, { "id": "3527", "type": "protein_family_or_group", "text": [ "TSHR" ], "offsets": [ [ 912, 916 ] ], "normalized": [] }, { "id": "3528", "type": "other_name", "text": [ "surgery" ], "offsets": [ [ 933, 940 ] ], "normalized": [] }, { "id": "3529", "type": "protein_domain_or_region", "text": [ "extracellular domain" ], "offsets": [ [ 982, 1002 ] ], "normalized": [] }, { "id": "3530", "type": "other_name", "text": [ "thyroidectomy" ], "offsets": [ [ 1034, 1047 ] ], "normalized": [] }, { "id": "3531", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 1063, 1071 ] ], "normalized": [] }, { "id": "3532", "type": "cell_type", "text": [ "PBMC" ], "offsets": [ [ 1073, 1077 ] ], "normalized": [] }, { "id": "3533", "type": "peptide", "text": [ "peptide" ], "offsets": [ [ 1096, 1103 ] ], "normalized": [] }, { "id": "3534", "type": "peptide", "text": [ "recognized peptides" ], "offsets": [ [ 1130, 1149 ] ], "normalized": [] }, { "id": "3535", "type": "other_name", "text": [ "T cell reactivity" ], "offsets": [ [ 1187, 1204 ] ], "normalized": [] }, { "id": "3536", "type": "protein_family_or_group", "text": [ "TSHR" ], "offsets": [ [ 1208, 1212 ] ], "normalized": [] }, { "id": "3537", "type": "other_name", "text": [ "surgery" ], "offsets": [ [ 1252, 1259 ] ], "normalized": [] }, { "id": "3538", "type": "cell_type", "text": [ "PBMC" ], "offsets": [ [ 1278, 1282 ] ], "normalized": [] }, { "id": "3539", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 1296, 1304 ] ], "normalized": [] }, { "id": "3540", "type": "other_name", "text": [ "RAI therapy" ], "offsets": [ [ 1312, 1323 ] ], "normalized": [] }, { "id": "3541", "type": "other_name", "text": [ "RAI therapy" ], "offsets": [ [ 1392, 1403 ] ], "normalized": [] }, { "id": "3542", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 1419, 1427 ] ], "normalized": [] }, { "id": "3543", "type": "peptide", "text": [ "peptide" ], "offsets": [ [ 1446, 1453 ] ], "normalized": [] }, { "id": "3544", "type": "other_name", "text": [ "RAI" ], "offsets": [ [ 1535, 1538 ] ], "normalized": [] }, { "id": "3545", "type": "other_name", "text": [ "T cell responses" ], "offsets": [ [ 1540, 1556 ] ], "normalized": [] }, { "id": "3546", "type": "peptide", "text": [ "TSHR peptides" ], "offsets": [ [ 1560, 1573 ] ], "normalized": [] }, { "id": "3547", "type": "protein_family_or_group", "text": [ "TSHR" ], "offsets": [ [ 1560, 1564 ] ], "normalized": [] }, { "id": "3548", "type": "other_name", "text": [ "RAI therapy" ], "offsets": [ [ 1611, 1622 ] ], "normalized": [] }, { "id": "3549", "type": "cell_type", "text": [ "PBMC" ], "offsets": [ [ 1680, 1684 ] ], "normalized": [] }, { "id": "3550", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 1690, 1698 ] ], "normalized": [] }, { "id": "3551", "type": "other_name", "text": [ "GD" ], "offsets": [ [ 1704, 1706 ] ], "normalized": [] }, { "id": "3552", "type": "other_organic_compound", "text": [ "ATD" ], "offsets": [ [ 1732, 1735 ] ], "normalized": [] }, { "id": "3553", "type": "other_name", "text": [ "surgery" ], "offsets": [ [ 1766, 1773 ] ], "normalized": [] }, { "id": "3554", "type": "other_name", "text": [ "RAI therapy" ], "offsets": [ [ 1777, 1788 ] ], "normalized": [] }, { "id": "3555", "type": "cell_line", "text": [ "T cell lines" ], "offsets": [ [ 1808, 1820 ] ], "normalized": [] }, { "id": "3556", "type": "cell_type", "text": [ "PBMC" ], "offsets": [ [ 1872, 1876 ] ], "normalized": [] }, { "id": "3557", "type": "protein_family_or_group", "text": [ "TSHR antibody" ], "offsets": [ [ 1894, 1907 ] ], "normalized": [] }, { "id": "3558", "type": "protein_family_or_group", "text": [ "TSHR" ], "offsets": [ [ 1894, 1898 ] ], "normalized": [] }, { "id": "3559", "type": "protein_family_or_group", "text": [ "microsomal antibody" ], "offsets": [ [ 1912, 1931 ] ], "normalized": [] }, { "id": "3560", "type": "other_name", "text": [ "surgery" ], "offsets": [ [ 1955, 1962 ] ], "normalized": [] }, { "id": "3561", "type": "other_name", "text": [ "RAI therapy" ], "offsets": [ [ 1984, 1995 ] ], "normalized": [] }, { "id": "3562", "type": "peptide", "text": [ "recognized peptides" ], "offsets": [ [ 2029, 2048 ] ], "normalized": [] }, { "id": "3563", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 2052, 2060 ] ], "normalized": [] }, { "id": "3564", "type": "cell_type", "text": [ "PBMC" ], "offsets": [ [ 2062, 2066 ] ], "normalized": [] }, { "id": "3565", "type": "other_name", "text": [ "RAI" ], "offsets": [ [ 2074, 2077 ] ], "normalized": [] }, { "id": "3566", "type": "other_name", "text": [ "surgery" ], "offsets": [ [ 2082, 2089 ] ], "normalized": [] }, { "id": "3567", "type": "other_organic_compound", "text": [ "ATD" ], "offsets": [ [ 2139, 2142 ] ], "normalized": [] }, { "id": "3568", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 2150, 2158 ] ], "normalized": [] }, { "id": "3569", "type": "other_name", "text": [ "RAI" ], "offsets": [ [ 2166, 2169 ] ], "normalized": [] }, { "id": "3570", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 2196, 2204 ] ], "normalized": [] }, { "id": "3571", "type": "other_name", "text": [ "surgery" ], "offsets": [ [ 2212, 2219 ] ], "normalized": [] }, { "id": "3572", "type": "other_name", "text": [ "T cell reactivity" ], "offsets": [ [ 2235, 2252 ] ], "normalized": [] }, { "id": "3573", "type": "protein_family_or_group", "text": [ "thyroid antigens" ], "offsets": [ [ 2256, 2272 ] ], "normalized": [] }, { "id": "3574", "type": "other_name", "text": [ "thyroidectomy" ], "offsets": [ [ 2279, 2292 ] ], "normalized": [] }, { "id": "3575", "type": "body_part", "text": [ "thyroid gland" ], "offsets": [ [ 2347, 2360 ] ], "normalized": [] }, { "id": "3576", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 2401, 2408 ] ], "normalized": [] }, { "id": "3577", "type": "other_name", "text": [ "T cell response" ], "offsets": [ [ 2424, 2439 ] ], "normalized": [] }, { "id": "3578", "type": "other_name", "text": [ "RAI therapy" ], "offsets": [ [ 2446, 2457 ] ], "normalized": [] }, { "id": "3579", "type": "other_name", "text": [ "RAI" ], "offsets": [ [ 2446, 2449 ] ], "normalized": [] }, { "id": "3580", "type": "other_name", "text": [ "epitope specific" ], "offsets": [ [ 2470, 2486 ] ], "normalized": [] }, { "id": "3581", "type": "protein_family_or_group", "text": [ "TSHR" ], "offsets": [ [ 2524, 2528 ] ], "normalized": [] }, { "id": "3582", "type": "other_name", "text": [ "Synchronous recognition" ], "offsets": [ [ 2539, 2562 ] ], "normalized": [] }, { "id": "3583", "type": "peptide", "text": [ "peptides 158-176" ], "offsets": [ [ 2566, 2582 ] ], "normalized": [] }, { "id": "3584", "type": "peptide", "text": [ "248-263" ], "offsets": [ [ 2587, 2594 ] ], "normalized": [] }, { "id": "3585", "type": "other_name", "text": [ "GD" ], "offsets": [ [ 2631, 2633 ] ], "normalized": [] }, { "id": "3586", "type": "protein_family_or_group", "text": [ "epitopes" ], "offsets": [ [ 2679, 2687 ] ], "normalized": [] }, { "id": "3587", "type": "other_name", "text": [ "immune remission" ], "offsets": [ [ 2712, 2728 ] ], "normalized": [] }, { "id": "3588", "type": "other_name", "text": [ "euthyroidism" ], "offsets": [ [ 2748, 2760 ] ], "normalized": [] } ]

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[ { "id": "3590", "type": "title", "text": [ "Circumvention of tolerance for the nuclear T cell protein TCF-1 by immunization of TCF-1 knock-out mice." ], "offsets": [ [ 0, 104 ] ] }, { "id": "3591", "type": "abstract", "text": [ "Molecular events that underlie the well-defined phenotypic changes of the differentiating thymocyte are poorly understood. A candidate gene to control thymocyte differentiation, T cell factor-1 (TCF-1)* encodes a DNA-binding protein. Its mRNA expression pattern is complex during embryogenesis, yet restricted to lymphocytes postnatally. Expression studies on TCF-1 protein have been hampered by the difficulty to raise antibodies due to extreme evolutionary conservation. TCF-1 knock-out mice, generated recently in our laboratory, have strongly decreased numbers of thymocytes, but are otherwise normal. We have used these mice to generate anti-TCF-1 antibodies. By immunization with a recombinant fusion protein, we show that TCF-1 knock-out mice readily yield antiserum titers against human and mouse TCF-1 protein. Wild-type littermates remain unresponsive to TCF-1 while they mount a high-titer antibody response to the fusion protein, Maltose Binding Protein (MBP). Subsequently, TCF-1-specific hybridomas could be prepared from the spleens of immunized knock-out mice. This study illustrates the almost complete tolerance of mice for human TCF-1 and demonstrates that this tolerance is readily broken by gene knock-out. Furthermore, the usefulness of knock-out mice for the generation of monoclonal antibodies against the gene product of interest is underscored." ], "offsets": [ [ 105, 1475 ] ] } ]

[ { "id": "3592", "type": "protein_family_or_group", "text": [ "nuclear T cell protein" ], "offsets": [ [ 35, 57 ] ], "normalized": [] }, { "id": "3593", "type": "protein_molecule", "text": [ "TCF-1" ], "offsets": [ [ 58, 63 ] ], "normalized": [] }, { "id": "3594", "type": "other_artificial_source", "text": [ "TCF-1 knock-out mice" ], "offsets": [ [ 83, 103 ] ], "normalized": [] }, { "id": "3595", "type": "protein_molecule", "text": [ "TCF-1" ], "offsets": [ [ 83, 88 ] ], "normalized": [] }, { "id": "3596", "type": "cell_type", "text": [ "differentiating thymocyte" ], "offsets": [ [ 179, 204 ] ], "normalized": [] }, { "id": "3597", "type": "other_name", "text": [ "thymocyte differentiation" ], "offsets": [ [ 256, 281 ] ], "normalized": [] }, { "id": "3598", "type": "cell_type", "text": [ "thymocyte" ], "offsets": [ [ 256, 265 ] ], "normalized": [] }, { "id": "3599", "type": "protein_molecule", "text": [ "T cell factor-1" ], "offsets": [ [ 283, 298 ] ], "normalized": [] }, { "id": "3600", "type": "protein_molecule", "text": [ "TCF-1" ], "offsets": [ [ 300, 305 ] ], "normalized": [] }, { "id": "3601", "type": "protein_family_or_group", "text": [ "DNA-binding protein" ], "offsets": [ [ 318, 337 ] ], "normalized": [] }, { "id": "3602", "type": "other_name", "text": [ "mRNA expression pattern" ], "offsets": [ [ 343, 366 ] ], "normalized": [] }, { "id": "3603", "type": "other_name", "text": [ "embryogenesis" ], "offsets": [ [ 385, 398 ] ], "normalized": [] }, { "id": "3604", "type": "cell_type", "text": [ "lymphocytes" ], "offsets": [ [ 418, 429 ] ], "normalized": [] }, { "id": "3605", "type": "protein_molecule", "text": [ "TCF-1 protein" ], "offsets": [ [ 465, 478 ] ], "normalized": [] }, { "id": "3606", "type": "protein_molecule", "text": [ "TCF-1" ], "offsets": [ [ 465, 470 ] ], "normalized": [] }, { "id": "3607", "type": "protein_family_or_group", "text": [ "antibodies" ], "offsets": [ [ 525, 535 ] ], "normalized": [] }, { "id": "3608", "type": "other_artificial_source", "text": [ "TCF-1 knock-out mice" ], "offsets": [ [ 578, 598 ] ], "normalized": [] }, { "id": "3609", "type": "protein_molecule", "text": [ "TCF-1" ], "offsets": [ [ 578, 583 ] ], "normalized": [] }, { "id": "3610", "type": "cell_type", "text": [ "thymocytes" ], "offsets": [ [ 673, 683 ] ], "normalized": [] }, { "id": "3611", "type": "protein_family_or_group", "text": [ "anti-TCF-1 antibodies" ], "offsets": [ [ 747, 768 ] ], "normalized": [] }, { "id": "3612", "type": "protein_molecule", "text": [ "TCF-1" ], "offsets": [ [ 752, 757 ] ], "normalized": [] }, { "id": "3613", "type": "protein_family_or_group", "text": [ "recombinant fusion protein" ], "offsets": [ [ 793, 819 ] ], "normalized": [] }, { "id": "3614", "type": "other_artificial_source", "text": [ "TCF-1 knock-out mice" ], "offsets": [ [ 834, 854 ] ], "normalized": [] }, { "id": "3615", "type": "protein_molecule", "text": [ "TCF-1" ], "offsets": [ [ 834, 839 ] ], "normalized": [] }, { "id": "3616", "type": "(AND protein_N/A protein_N/A)", "text": [ "human and mouse TCF-1 protein" ], "offsets": [ [ 894, 923 ] ], "normalized": [] }, { "id": "3617", "type": "", "text": [ "human" ], "offsets": [ [ 894, 899 ] ], "normalized": [] }, { "id": "3618", "type": "", "text": [ "mouse" ], "offsets": [ [ 904, 909 ] ], "normalized": [] }, { "id": "3619", "type": "", "text": [ "TCF-1 protein" ], "offsets": [ [ 910, 923 ] ], "normalized": [] }, { "id": "3620", "type": "protein_molecule", "text": [ "TCF-1" ], "offsets": [ [ 970, 975 ] ], "normalized": [] }, { "id": "3621", "type": "other_name", "text": [ "high-titer antibody response" ], "offsets": [ [ 995, 1023 ] ], "normalized": [] }, { "id": "3622", "type": "protein_family_or_group", "text": [ "fusion protein" ], "offsets": [ [ 1031, 1045 ] ], "normalized": [] }, { "id": "3623", "type": "protein_molecule", "text": [ "Maltose Binding Protein" ], "offsets": [ [ 1047, 1070 ] ], "normalized": [] }, { "id": "3624", "type": "protein_molecule", "text": [ "MBP" ], "offsets": [ [ 1072, 1075 ] ], "normalized": [] }, { "id": "3625", "type": "cell_line", "text": [ "TCF-1-specific hybridomas" ], "offsets": [ [ 1092, 1117 ] ], "normalized": [] }, { "id": "3626", "type": "protein_molecule", "text": [ "TCF-1" ], "offsets": [ [ 1092, 1097 ] ], "normalized": [] }, { "id": "3627", "type": "body_part", "text": [ "spleens" ], "offsets": [ [ 1145, 1152 ] ], "normalized": [] }, { "id": "3628", "type": "other_artificial_source", "text": [ "immunized knock-out mice" ], "offsets": [ [ 1156, 1180 ] ], "normalized": [] }, { "id": "3629", "type": "multi_cell", "text": [ "mice" ], "offsets": [ [ 1238, 1242 ] ], "normalized": [] }, { "id": "3630", "type": "protein_molecule", "text": [ "human TCF-1" ], "offsets": [ [ 1247, 1258 ] ], "normalized": [] }, { "id": "3631", "type": "protein_molecule", "text": [ "TCF-1" ], "offsets": [ [ 1253, 1258 ] ], "normalized": [] }, { "id": "3632", "type": "other_name", "text": [ "gene knock-out" ], "offsets": [ [ 1317, 1331 ] ], "normalized": [] }, { "id": "3633", "type": "other_artificial_source", "text": [ "knock-out mice" ], "offsets": [ [ 1364, 1378 ] ], "normalized": [] }, { "id": "3634", "type": "protein_family_or_group", "text": [ "monoclonal antibodies" ], "offsets": [ [ 1401, 1422 ] ], "normalized": [] } ]

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[ { "id": "3636", "type": "title", "text": [ "The transcription factor, Nm23H2, binds to and activates the translocated c-myc allele in Burkitt's lymphoma." ], "offsets": [ [ 0, 109 ] ] }, { "id": "3637", "type": "abstract", "text": [ "We have identified an in vivo footprint over the PuF site on the translocated c-myc allele in Burkitt's lymphoma cells. The PuF site on the silent normal c-myc allele was unoccupied. We demonstrated by electrophoretic mobility shift assay, electrophoretic mobility shift assay with antibody, UV cross-linking followed by SDS-gel electrophoresis, and Western analysis that Nm23H2 in B cell nuclear extracts bound to the c-myc PuF site. Transfection experiments with c-myc promoter constructs in both DHL-9 and Raji cells revealed that the PuF site functioned as a positive regulatory element in B cells with a drop in activity with mutation of this site. Access to this site is blocked in the normal silent c-myc allele; these data suggest that the Nm23H2 protein is involved in deregulation of the translocated c-myc allele in Burkitt's lymphoma cells." ], "offsets": [ [ 110, 962 ] ] } ]

[ { "id": "3638", "type": "protein_family_or_group", "text": [ "transcription factor" ], "offsets": [ [ 4, 24 ] ], "normalized": [] }, { "id": "3639", "type": "protein_molecule", "text": [ "Nm23H2" ], "offsets": [ [ 26, 32 ] ], "normalized": [] }, { "id": "3640", "type": "DNA_domain_or_region", "text": [ "c-myc allele" ], "offsets": [ [ 74, 86 ] ], "normalized": [] }, { "id": "3641", "type": "other_name", "text": [ "Burkitt's lymphoma" ], "offsets": [ [ 90, 108 ] ], "normalized": [] }, { "id": "3642", "type": "other_name", "text": [ "in vivo footprint" ], "offsets": [ [ 132, 149 ] ], "normalized": [] }, { "id": "3643", "type": "DNA_domain_or_region", "text": [ "PuF site" ], "offsets": [ [ 159, 167 ] ], "normalized": [] }, { "id": "3644", "type": "DNA_domain_or_region", "text": [ "c-myc allele" ], "offsets": [ [ 188, 200 ] ], "normalized": [] }, { "id": "3645", "type": "other_name", "text": [ "Burkitt's lymphoma" ], "offsets": [ [ 204, 222 ] ], "normalized": [] }, { "id": "3646", "type": "DNA_domain_or_region", "text": [ "PuF site" ], "offsets": [ [ 234, 242 ] ], "normalized": [] }, { "id": "3647", "type": "DNA_domain_or_region", "text": [ "silent normal c-myc allele" ], "offsets": [ [ 250, 276 ] ], "normalized": [] }, { "id": "3648", "type": "DNA_domain_or_region", "text": [ "c-myc allele" ], "offsets": [ [ 264, 276 ] ], "normalized": [] }, { "id": "3649", "type": "other_name", "text": [ "electrophoretic mobility shift assay" ], "offsets": [ [ 312, 348 ] ], "normalized": [] }, { "id": "3650", "type": "other_name", "text": [ "electrophoretic mobility shift assay" ], "offsets": [ [ 350, 386 ] ], "normalized": [] }, { "id": "3651", "type": "other_name", "text": [ "UV cross-linking" ], "offsets": [ [ 402, 418 ] ], "normalized": [] }, { "id": "3652", "type": "other_name", "text": [ "SDS-gel electrophoresis" ], "offsets": [ [ 431, 454 ] ], "normalized": [] }, { "id": "3653", "type": "other_name", "text": [ "Western analysis" ], "offsets": [ [ 460, 476 ] ], "normalized": [] }, { "id": "3654", "type": "protein_molecule", "text": [ "Nm23H2" ], "offsets": [ [ 482, 488 ] ], "normalized": [] }, { "id": "3655", "type": "cell_component", "text": [ "B cell nuclear extracts" ], "offsets": [ [ 492, 515 ] ], "normalized": [] }, { "id": "3656", "type": "DNA_domain_or_region", "text": [ "PuF site" ], "offsets": [ [ 535, 543 ] ], "normalized": [] }, { "id": "3657", "type": "DNA_family_or_group", "text": [ "c-myc promoter constructs" ], "offsets": [ [ 575, 600 ] ], "normalized": [] }, { "id": "3658", "type": "DNA_domain_or_region", "text": [ "c-myc promoter" ], "offsets": [ [ 575, 589 ] ], "normalized": [] }, { "id": "3659", "type": "cell_line", "text": [ "DHL-9" ], "offsets": [ [ 609, 614 ] ], "normalized": [] }, { "id": "3660", "type": "cell_line", "text": [ "Raji cells" ], "offsets": [ [ 619, 629 ] ], "normalized": [] }, { "id": "3661", "type": "DNA_domain_or_region", "text": [ "PuF site" ], "offsets": [ [ 648, 656 ] ], "normalized": [] }, { "id": "3662", "type": "DNA_family_or_group", "text": [ "positive regulatory element" ], "offsets": [ [ 673, 700 ] ], "normalized": [] }, { "id": "3663", "type": "cell_type", "text": [ "B cells" ], "offsets": [ [ 704, 711 ] ], "normalized": [] }, { "id": "3664", "type": "DNA_domain_or_region", "text": [ "normal silent c-myc allele" ], "offsets": [ [ 802, 828 ] ], "normalized": [] }, { "id": "3665", "type": "DNA_domain_or_region", "text": [ "c-myc allele" ], "offsets": [ [ 816, 828 ] ], "normalized": [] }, { "id": "3666", "type": "protein_molecule", "text": [ "Nm23H2" ], "offsets": [ [ 858, 864 ] ], "normalized": [] }, { "id": "3667", "type": "DNA_domain_or_region", "text": [ "c-myc allele" ], "offsets": [ [ 921, 933 ] ], "normalized": [] }, { "id": "3668", "type": "cell_line", "text": [ "Burkitt's lymphoma cells" ], "offsets": [ [ 937, 961 ] ], "normalized": [] }, { "id": "3669", "type": "other_name", "text": [ "Burkitt's lymphoma" ], "offsets": [ [ 937, 955 ] ], "normalized": [] } ]

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[ { "id": "3671", "type": "title", "text": [ "Identification of two novel regulatory elements within the 5'-untranslated region of the human A gamma-globin gene." ], "offsets": [ [ 0, 115 ] ] }, { "id": "3672", "type": "abstract", "text": [ "Interaction between the stage selector element (SSE) in the proximal gamma-globin promoter and hypersensitivity site 2 in the locus control region partly mediates the competitive silencing of the beta-globin promoter in the fetal developmental stage. We have now demonstrated that a second SSE-like element in the 5'-untranslated region of the gamma-gene also contributes to this competitive silencing of the beta-gene. Utilizing transient transfection assays in the fetal erythroid cell line, K562, we have shown that the core enhancer of hypersensitivity site 2 can preferentially interact with the proximal gamma-promoter in the absence of the SSE, completely silencing a linked beta-promoter. Mutation of a 20-base pair sequence of the gamma-gene 5'-untranslated region (UTR) led to derepression of beta-promoter activity. A marked activation of gamma-promoter activity was also observed with this mutation, suggesting the presence of a repressor. Fine mutagenesis dissected these activities to different regions of the 5'-UTR. The stage selector activity was localized to a region centered on nucleotides +13 to +15. Electromobility shift assays utilizing this sequence demonstrated binding of a fetal and erythroid-specific protein. The repressor activity of the 5'-UTR was localized to tandem GATA-like sites, which appear to bind a complex of two proteins, one of which is the erythroid transcription factor GATA-1. These results indicate that the 5'-UTR of the gamma-gene contains sequences that may be important for its transcriptional and developmental regulation." ], "offsets": [ [ 116, 1691 ] ] } ]

[ { "id": "3673", "type": "DNA_family_or_group", "text": [ "regulatory elements" ], "offsets": [ [ 28, 47 ] ], "normalized": [] }, { "id": "3674", "type": "DNA_domain_or_region", "text": [ "5'-untranslated region" ], "offsets": [ [ 59, 81 ] ], "normalized": [] }, { "id": "3675", "type": "DNA_domain_or_region", "text": [ "human A gamma-globin gene" ], "offsets": [ [ 89, 114 ] ], "normalized": [] }, { "id": "3676", "type": "DNA_domain_or_region", "text": [ "stage selector element" ], "offsets": [ [ 140, 162 ] ], "normalized": [] }, { "id": "3677", "type": "DNA_substructure", "text": [ "SSE" ], "offsets": [ [ 164, 167 ] ], "normalized": [] }, { "id": "3678", "type": "DNA_domain_or_region", "text": [ "proximal gamma-globin promoter" ], "offsets": [ [ 176, 206 ] ], "normalized": [] }, { "id": "3679", "type": "DNA_domain_or_region", "text": [ "hypersensitivity site 2" ], "offsets": [ [ 211, 234 ] ], "normalized": [] }, { "id": "3680", "type": "DNA_domain_or_region", "text": [ "locus control region" ], "offsets": [ [ 242, 262 ] ], "normalized": [] }, { "id": "3681", "type": "DNA_domain_or_region", "text": [ "beta-globin promoter" ], "offsets": [ [ 312, 332 ] ], "normalized": [] }, { "id": "3682", "type": "DNA_domain_or_region", "text": [ "SSE-like element" ], "offsets": [ [ 406, 422 ] ], "normalized": [] }, { "id": "3683", "type": "DNA_domain_or_region", "text": [ "5'-untranslated region" ], "offsets": [ [ 430, 452 ] ], "normalized": [] }, { "id": "3684", "type": "DNA_domain_or_region", "text": [ "gamma-gene" ], "offsets": [ [ 460, 470 ] ], "normalized": [] }, { "id": "3685", "type": "DNA_domain_or_region", "text": [ "beta-gene" ], "offsets": [ [ 525, 534 ] ], "normalized": [] }, { "id": "3686", "type": "other_name", "text": [ "transient transfection assays" ], "offsets": [ [ 546, 575 ] ], "normalized": [] }, { "id": "3687", "type": "cell_line", "text": [ "fetal erythroid cell line" ], "offsets": [ [ 583, 608 ] ], "normalized": [] }, { "id": "3688", "type": "cell_line", "text": [ "K562" ], "offsets": [ [ 610, 614 ] ], "normalized": [] }, { "id": "3689", "type": "DNA_domain_or_region", "text": [ "core enhancer" ], "offsets": [ [ 639, 652 ] ], "normalized": [] }, { "id": "3690", "type": "DNA_domain_or_region", "text": [ "hypersensitivity site 2" ], "offsets": [ [ 656, 679 ] ], "normalized": [] }, { "id": "3691", "type": "DNA_domain_or_region", "text": [ "proximal gamma-promoter" ], "offsets": [ [ 717, 740 ] ], "normalized": [] }, { "id": "3692", "type": "DNA_domain_or_region", "text": [ "SSE" ], "offsets": [ [ 763, 766 ] ], "normalized": [] }, { "id": "3693", "type": "DNA_domain_or_region", "text": [ "linked beta-promoter" ], "offsets": [ [ 791, 811 ] ], "normalized": [] }, { "id": "3694", "type": "DNA_domain_or_region", "text": [ "gamma-gene 5'-untranslated region" ], "offsets": [ [ 856, 889 ] ], "normalized": [] }, { "id": "3695", "type": "DNA_domain_or_region", "text": [ "UTR" ], "offsets": [ [ 891, 894 ] ], "normalized": [] }, { "id": "3696", "type": "other_name", "text": [ "beta-promoter activity" ], "offsets": [ [ 919, 941 ] ], "normalized": [] }, { "id": "3697", "type": "DNA_domain_or_region", "text": [ "beta-promoter" ], "offsets": [ [ 919, 932 ] ], "normalized": [] }, { "id": "3698", "type": "other_name", "text": [ "gamma-promoter activity" ], "offsets": [ [ 966, 989 ] ], "normalized": [] }, { "id": "3699", "type": "DNA_domain_or_region", "text": [ "gamma-promoter" ], "offsets": [ [ 966, 980 ] ], "normalized": [] }, { "id": "3700", "type": "other_name", "text": [ "mutation" ], "offsets": [ [ 1018, 1026 ] ], "normalized": [] }, { "id": "3701", "type": "other_name", "text": [ "mutagenesis" ], "offsets": [ [ 1073, 1084 ] ], "normalized": [] }, { "id": "3702", "type": "DNA_domain_or_region", "text": [ "5'-UTR" ], "offsets": [ [ 1140, 1146 ] ], "normalized": [] }, { "id": "3703", "type": "other_name", "text": [ "stage selector activity" ], "offsets": [ [ 1152, 1175 ] ], "normalized": [] }, { "id": "3704", "type": "DNA_domain_or_region", "text": [ "nucleotides +13 to +15" ], "offsets": [ [ 1214, 1236 ] ], "normalized": [] }, { "id": "3705", "type": "other_name", "text": [ "Electromobility shift assays" ], "offsets": [ [ 1238, 1266 ] ], "normalized": [] }, { "id": "3706", "type": "(AND protein_family_or_group protein_family_or_group)", "text": [ "fetal and erythroid-specific protein" ], "offsets": [ [ 1317, 1353 ] ], "normalized": [] }, { "id": "3707", "type": "", "text": [ "fetal" ], "offsets": [ [ 1317, 1322 ] ], "normalized": [] }, { "id": "3708", "type": "", "text": [ "erythroid" ], "offsets": [ [ 1327, 1336 ] ], "normalized": [] }, { "id": "3709", "type": "", "text": [ "-specific protein" ], "offsets": [ [ 1336, 1353 ] ], "normalized": [] }, { "id": "3710", "type": "other_name", "text": [ "repressor activity" ], "offsets": [ [ 1359, 1377 ] ], "normalized": [] }, { "id": "3711", "type": "DNA_domain_or_region", "text": [ "5'-UTR" ], "offsets": [ [ 1385, 1391 ] ], "normalized": [] }, { "id": "3712", "type": "DNA_family_or_group", "text": [ "GATA-like sites" ], "offsets": [ [ 1416, 1431 ] ], "normalized": [] }, { "id": "3713", "type": "protein_family_or_group", "text": [ "erythroid transcription factor" ], "offsets": [ [ 1501, 1531 ] ], "normalized": [] }, { "id": "3714", "type": "protein_family_or_group", "text": [ "transcription factor" ], "offsets": [ [ 1511, 1531 ] ], "normalized": [] }, { "id": "3715", "type": "protein_molecule", "text": [ "GATA-1" ], "offsets": [ [ 1532, 1538 ] ], "normalized": [] }, { "id": "3716", "type": "DNA_domain_or_region", "text": [ "5'-UTR" ], "offsets": [ [ 1572, 1578 ] ], "normalized": [] }, { "id": "3717", "type": "DNA_domain_or_region", "text": [ "gamma-gene" ], "offsets": [ [ 1586, 1596 ] ], "normalized": [] }, { "id": "3718", "type": "other_name", "text": [ "transcriptional and developmental regulation" ], "offsets": [ [ 1646, 1690 ] ], "normalized": [] }, { "id": "3719", "type": "other_name", "text": [ "transcriptional" ], "offsets": [ [ 1646, 1661 ] ], "normalized": [] }, { "id": "3720", "type": "other_name", "text": [ "developmental regulation" ], "offsets": [ [ 1666, 1690 ] ], "normalized": [] } ]

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[ { "id": "3722", "type": "title", "text": [ "Coupling of a signal response domain in I kappa B alpha to multiple pathways for NF-kappa B activation." ], "offsets": [ [ 0, 103 ] ] }, { "id": "3723", "type": "abstract", "text": [ "The eukaryotic transcription factor NF-kappa B plays a central role in the induced expression of human immunodeficiency virus type 1 and in many aspects of the genetic program mediating normal T-cell activation and growth. The nuclear activity of NF-kappa B is tightly regulated from the cytoplasmic compartment by an inhibitory subunit called I kappa B alpha. This cytoplasmic inhibitor is rapidly phosphorylated and degraded in response to a diverse set of NF-kappa B-inducing agents, including T-cell mitogens, proinflammatory cytokines, and viral transactivators such as the Tax protein of human T-cell leukemia virus type 1. To explore these I kappa B alpha-dependent mechanisms for NF-kappa B induction, we identified novel mutants of I kappa B alpha that uncouple its inhibitory and signal-transducing functions in human T lymphocytes. Specifically, removal of the N-terminal 36 amino acids of I kappa B alpha failed to disrupt its ability to form latent complexes with NF-kappa B in the cytoplasm. However, this deletion mutation prevented the induced phosphorylation, degradative loss, and functional release of I kappa B alpha from NF-kappa B in Tax-expressing cells. Alanine substitutions introduced at two serine residues positioned within this N-terminal regulatory region of I kappa B alpha also yielded constitutive repressors that escaped from Tax-induced turnover and that potently inhibited immune activation pathways for NF-kappa B induction, including those initiated from antigen and cytokine receptors. In contrast, introduction of a phosphoserine mimetic at these sites rectified this functional defect, a finding consistent with a causal linkage between the phosphorylation status and proteolytic stability of this cytoplasmic inhibitor. Together, these in vivo studies define a critical signal response domain in I kappa B alpha that coordinately controls the biologic activities of I kappa B alpha and NF-kappa B in response to viral and immune stimuli." ], "offsets": [ [ 104, 2083 ] ] } ]

[ { "id": "3724", "type": "protein_domain_or_region", "text": [ "signal response domain" ], "offsets": [ [ 14, 36 ] ], "normalized": [] }, { "id": "3725", "type": "protein_molecule", "text": [ "I kappa B alpha" ], "offsets": [ [ 40, 55 ] ], "normalized": [] }, { "id": "3726", "type": "other_name", "text": [ "multiple pathways" ], "offsets": [ [ 59, 76 ] ], "normalized": [] }, { "id": "3727", "type": "other_name", "text": [ "NF-kappa B activation" ], "offsets": [ [ 81, 102 ] ], "normalized": [] }, { "id": "3728", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 81, 91 ] ], "normalized": [] }, { "id": "3729", "type": "protein_family_or_group", "text": [ "eukaryotic transcription factor" ], "offsets": [ [ 108, 139 ] ], "normalized": [] }, { "id": "3730", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 140, 150 ] ], "normalized": [] }, { "id": "3731", "type": "virus", "text": [ "human immunodeficiency virus type 1" ], "offsets": [ [ 201, 236 ] ], "normalized": [] }, { "id": "3732", "type": "other_name", "text": [ "normal T-cell activation" ], "offsets": [ [ 290, 314 ] ], "normalized": [] }, { "id": "3733", "type": "other_name", "text": [ "growth" ], "offsets": [ [ 319, 325 ] ], "normalized": [] }, { "id": "3734", "type": "other_name", "text": [ "nuclear activity" ], "offsets": [ [ 331, 347 ] ], "normalized": [] }, { "id": "3735", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 351, 361 ] ], "normalized": [] }, { "id": "3736", "type": "cell_component", "text": [ "cytoplasmic compartment" ], "offsets": [ [ 392, 415 ] ], "normalized": [] }, { "id": "3737", "type": "protein_subunit", "text": [ "inhibitory subunit" ], "offsets": [ [ 422, 440 ] ], "normalized": [] }, { "id": "3738", "type": "protein_subunit", "text": [ "I kappa B alpha" ], "offsets": [ [ 448, 463 ] ], "normalized": [] }, { "id": "3739", "type": "protein_family_or_group", "text": [ "NF-kappa B-inducing agents" ], "offsets": [ [ 563, 589 ] ], "normalized": [] }, { "id": "3740", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 563, 573 ] ], "normalized": [] }, { "id": "3741", "type": "protein_family_or_group", "text": [ "T-cell mitogens," ], "offsets": [ [ 601, 617 ] ], "normalized": [] }, { "id": "3742", "type": "protein_family_or_group", "text": [ "proinflammatory cytokines" ], "offsets": [ [ 618, 643 ] ], "normalized": [] }, { "id": "3743", "type": "protein_family_or_group", "text": [ "viral transactivators" ], "offsets": [ [ 649, 670 ] ], "normalized": [] }, { "id": "3744", "type": "protein_molecule", "text": [ "Tax protein" ], "offsets": [ [ 683, 694 ] ], "normalized": [] }, { "id": "3745", "type": "virus", "text": [ "human T-cell leukemia virus type 1" ], "offsets": [ [ 698, 732 ] ], "normalized": [] }, { "id": "3746", "type": "other_name", "text": [ "I kappa B alpha-dependent mechanisms" ], "offsets": [ [ 751, 787 ] ], "normalized": [] }, { "id": "3747", "type": "protein_subunit", "text": [ "I kappa B alpha" ], "offsets": [ [ 751, 766 ] ], "normalized": [] }, { "id": "3748", "type": "other_name", "text": [ "NF-kappa B induction" ], "offsets": [ [ 792, 812 ] ], "normalized": [] }, { "id": "3749", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 792, 802 ] ], "normalized": [] }, { "id": "3750", "type": "protein_molecule", "text": [ "I kappa B alpha" ], "offsets": [ [ 751, 766 ] ], "normalized": [] }, { "id": "3751", "type": "cell_type", "text": [ "human T lymphocytes" ], "offsets": [ [ 926, 945 ] ], "normalized": [] }, { "id": "3752", "type": "cell_type", "text": [ "T lymphocytes" ], "offsets": [ [ 932, 945 ] ], "normalized": [] }, { "id": "3753", "type": "protein_domain_or_region", "text": [ "N-terminal 36 amino acids" ], "offsets": [ [ 976, 1001 ] ], "normalized": [] }, { "id": "3754", "type": "protein_molecule", "text": [ "I kappa B alpha" ], "offsets": [ [ 1005, 1020 ] ], "normalized": [] }, { "id": "3755", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 1081, 1091 ] ], "normalized": [] }, { "id": "3756", "type": "cell_component", "text": [ "cytoplasm" ], "offsets": [ [ 1099, 1108 ] ], "normalized": [] }, { "id": "3757", "type": "other_name", "text": [ "mutation" ], "offsets": [ [ 1133, 1141 ] ], "normalized": [] }, { "id": "3758", "type": "other_name", "text": [ "phosphorylation" ], "offsets": [ [ 1164, 1179 ] ], "normalized": [] }, { "id": "3759", "type": "other_name", "text": [ "degradative loss" ], "offsets": [ [ 1181, 1197 ] ], "normalized": [] }, { "id": "3760", "type": "protein_molecule", "text": [ "I kappa B alpha" ], "offsets": [ [ 1225, 1240 ] ], "normalized": [] }, { "id": "3761", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 1246, 1256 ] ], "normalized": [] }, { "id": "3762", "type": "cell_line", "text": [ "Tax-expressing cells" ], "offsets": [ [ 1260, 1280 ] ], "normalized": [] }, { "id": "3763", "type": "protein_molecule", "text": [ "Tax" ], "offsets": [ [ 1260, 1263 ] ], "normalized": [] }, { "id": "3764", "type": "amino_acid_monomer", "text": [ "serine residues" ], "offsets": [ [ 1322, 1337 ] ], "normalized": [] }, { "id": "3765", "type": "protein_domain_or_region", "text": [ "N-terminal regulatory region" ], "offsets": [ [ 1361, 1389 ] ], "normalized": [] }, { "id": "3766", "type": "protein_molecule", "text": [ "I kappa B alpha" ], "offsets": [ [ 1393, 1408 ] ], "normalized": [] }, { "id": "3767", "type": "other_name", "text": [ "Tax-induced turnover" ], "offsets": [ [ 1464, 1484 ] ], "normalized": [] }, { "id": "3768", "type": "protein_molecule", "text": [ "Tax" ], "offsets": [ [ 1464, 1467 ] ], "normalized": [] }, { "id": "3769", "type": "other_name", "text": [ "immune activation pathways" ], "offsets": [ [ 1513, 1539 ] ], "normalized": [] }, { "id": "3770", "type": "other_name", "text": [ "NF-kappa B induction" ], "offsets": [ [ 1544, 1564 ] ], "normalized": [] }, { "id": "3771", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 1544, 1554 ] ], "normalized": [] }, { "id": "3772", "type": "(AND protein_family_or_group protein_family_or_group)", "text": [ "antigen and cytokine receptors" ], "offsets": [ [ 1597, 1627 ] ], "normalized": [] }, { "id": "3773", "type": "", "text": [ "antigen" ], "offsets": [ [ 1597, 1604 ] ], "normalized": [] }, { "id": "3774", "type": "", "text": [ "cytokine" ], "offsets": [ [ 1609, 1617 ] ], "normalized": [] }, { "id": "3775", "type": "", "text": [ "receptors" ], "offsets": [ [ 1618, 1627 ] ], "normalized": [] }, { "id": "3776", "type": "amino_acid_monomer", "text": [ "phosphoserine mimetic" ], "offsets": [ [ 1660, 1681 ] ], "normalized": [] }, { "id": "3777", "type": "other_name", "text": [ "phosphorylation status" ], "offsets": [ [ 1786, 1808 ] ], "normalized": [] }, { "id": "3778", "type": "other_name", "text": [ "proteolytic stability" ], "offsets": [ [ 1813, 1834 ] ], "normalized": [] }, { "id": "3779", "type": "protein_family_or_group", "text": [ "cytoplasmic inhibitor" ], "offsets": [ [ 1843, 1864 ] ], "normalized": [] }, { "id": "3780", "type": "protein_molecule", "text": [ "I kappa B alpha" ], "offsets": [ [ 1942, 1957 ] ], "normalized": [] }, { "id": "3781", "type": "protein_molecule", "text": [ "I kappa B alpha" ], "offsets": [ [ 2012, 2027 ] ], "normalized": [] }, { "id": "3782", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 2032, 2042 ] ], "normalized": [] }, { "id": "3783", "type": "(AND other_name other_name)", "text": [ "viral and immune stimuli" ], "offsets": [ [ 2058, 2082 ] ], "normalized": [] }, { "id": "3784", "type": "", "text": [ "viral" ], "offsets": [ [ 2058, 2063 ] ], "normalized": [] }, { "id": "3785", "type": "", "text": [ "immune" ], "offsets": [ [ 2068, 2074 ] ], "normalized": [] }, { "id": "3786", "type": "", "text": [ "stimuli" ], "offsets": [ [ 2075, 2082 ] ], "normalized": [] } ]

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[ { "id": "3788", "type": "title", "text": [ "Growth regulation and cellular changes during differentiation of human prostatic cancer LNCaP cells as induced by T lymphocyte-conditioned medium." ], "offsets": [ [ 0, 146 ] ] }, { "id": "3789", "type": "abstract", "text": [ "Human prostatic epithelial cells from an androgen-dependent LNCaP cell line were examined in response to conditioned medium (CM) derived from phytohemagglutinin (PHA)-stimulated lymphocytes. Addition of CM caused a greater than 70% reduction of cell proliferation by cell counting and cell cycle. These cells showed G1 phase arrest and the clonogenicity was reduced. The growth-modulating effect was dose-dependent and not due to cell lysis or apoptosis. The binding of androgen to androgen receptor on these cells showed approximately 50% reduction, underlining a proliferation reduction mechanism. The prostate-specific antigen (PSA) was downregulated to approximately 75% during the process. Cell morphology showed dendritic processes extending from cytoplasm and other neuroendocrine cell characteristics. The expression of several cytoskeleton and intracellular proteins increased as determined by immunostaining on slides and by ELISA procedures. These included vimentin, correlating to cell shape changes, cytokeratins 8 and 18, associated with differentiated cell types of prostate epithelia, and neuron-specific enolase and serotonin, associated with neuroendocrine cells. From these cellular changes, we can infer that the cell growth was modulated along with induction of terminal differentiation. Activated T cells were demonstrated to be important in providing the modulating activity. This growth modulator was semipurified and had an estimated molecular weight 13,000 to 24,000 Da. The activity was determined to be distinct from TGF, TNF, and some commonly known lymphokines. The interaction between lymphoid and prostatic cells in growth and development is described." ], "offsets": [ [ 147, 1831 ] ] } ]

[ { "id": "3790", "type": "other_name", "text": [ "Growth regulation" ], "offsets": [ [ 0, 17 ] ], "normalized": [] }, { "id": "3791", "type": "other_name", "text": [ "cellular changes" ], "offsets": [ [ 22, 38 ] ], "normalized": [] }, { "id": "3792", "type": "cell_line", "text": [ "human prostatic cancer LNCaP cells" ], "offsets": [ [ 65, 99 ] ], "normalized": [] }, { "id": "3793", "type": "other_name", "text": [ "prostatic cancer" ], "offsets": [ [ 71, 87 ] ], "normalized": [] }, { "id": "3794", "type": "cell_line", "text": [ "LNCaP cells" ], "offsets": [ [ 88, 99 ] ], "normalized": [] }, { "id": "3795", "type": "other_organic_compound", "text": [ "T lymphocyte-conditioned medium" ], "offsets": [ [ 114, 145 ] ], "normalized": [] }, { "id": "3796", "type": "cell_line", "text": [ "Human prostatic epithelial cells" ], "offsets": [ [ 147, 179 ] ], "normalized": [] }, { "id": "3797", "type": "cell_line", "text": [ "androgen-dependent LNCaP cell line" ], "offsets": [ [ 188, 222 ] ], "normalized": [] }, { "id": "3798", "type": "other_organic_compound", "text": [ "conditioned medium" ], "offsets": [ [ 252, 270 ] ], "normalized": [] }, { "id": "3799", "type": "other_organic_compound", "text": [ "CM" ], "offsets": [ [ 272, 274 ] ], "normalized": [] }, { "id": "3800", "type": "cell_line", "text": [ "phytohemagglutinin (PHA)-stimulated lymphocytes" ], "offsets": [ [ 289, 336 ] ], "normalized": [] }, { "id": "3801", "type": "protein_molecule", "text": [ "phytohemagglutinin" ], "offsets": [ [ 289, 307 ] ], "normalized": [] }, { "id": "3802", "type": "protein_molecule", "text": [ "PHA" ], "offsets": [ [ 309, 312 ] ], "normalized": [] }, { "id": "3803", "type": "cell_type", "text": [ "lymphocytes" ], "offsets": [ [ 325, 336 ] ], "normalized": [] }, { "id": "3804", "type": "other_organic_compound", "text": [ "CM" ], "offsets": [ [ 350, 352 ] ], "normalized": [] }, { "id": "3805", "type": "other_name", "text": [ "cell proliferation" ], "offsets": [ [ 392, 410 ] ], "normalized": [] }, { "id": "3806", "type": "other_name", "text": [ "cell counting" ], "offsets": [ [ 414, 427 ] ], "normalized": [] }, { "id": "3807", "type": "other_name", "text": [ "cell cycle" ], "offsets": [ [ 432, 442 ] ], "normalized": [] }, { "id": "3808", "type": "other_name", "text": [ "G1 phase arrest" ], "offsets": [ [ 463, 478 ] ], "normalized": [] }, { "id": "3809", "type": "other_name", "text": [ "clonogenicity" ], "offsets": [ [ 487, 500 ] ], "normalized": [] }, { "id": "3810", "type": "other_name", "text": [ "dose-dependent" ], "offsets": [ [ 547, 561 ] ], "normalized": [] }, { "id": "3811", "type": "other_name", "text": [ "cell lysis" ], "offsets": [ [ 577, 587 ] ], "normalized": [] }, { "id": "3812", "type": "other_name", "text": [ "apoptosis" ], "offsets": [ [ 591, 600 ] ], "normalized": [] }, { "id": "3813", "type": "lipid", "text": [ "androgen" ], "offsets": [ [ 617, 625 ] ], "normalized": [] }, { "id": "3814", "type": "protein_family_or_group", "text": [ "androgen receptor" ], "offsets": [ [ 629, 646 ] ], "normalized": [] }, { "id": "3815", "type": "lipid", "text": [ "androgen" ], "offsets": [ [ 629, 637 ] ], "normalized": [] }, { "id": "3816", "type": "other_name", "text": [ "proliferation reduction mechanism" ], "offsets": [ [ 712, 745 ] ], "normalized": [] }, { "id": "3817", "type": "protein_molecule", "text": [ "prostate-specific antigen" ], "offsets": [ [ 751, 776 ] ], "normalized": [] }, { "id": "3818", "type": "protein_molecule", "text": [ "PSA" ], "offsets": [ [ 778, 781 ] ], "normalized": [] }, { "id": "3819", "type": "other_name", "text": [ "Cell morphology" ], "offsets": [ [ 842, 857 ] ], "normalized": [] }, { "id": "3820", "type": "cell_component", "text": [ "cytoplasm" ], "offsets": [ [ 900, 909 ] ], "normalized": [] }, { "id": "3821", "type": "other_name", "text": [ "neuroendocrine cell characteristics" ], "offsets": [ [ 920, 955 ] ], "normalized": [] }, { "id": "3822", "type": "cell_type", "text": [ "neuroendocrine cell" ], "offsets": [ [ 920, 939 ] ], "normalized": [] }, { "id": "3823", "type": "(AND protein_family_or_group protein_family_or_group)", "text": [ "cytoskeleton and intracellular proteins" ], "offsets": [ [ 983, 1022 ] ], "normalized": [] }, { "id": "3824", "type": "", "text": [ "cytoskeleton" ], "offsets": [ [ 983, 995 ] ], "normalized": [] }, { "id": "3825", "type": "", "text": [ "intracellular" ], "offsets": [ [ 1000, 1013 ] ], "normalized": [] }, { "id": "3826", "type": "", "text": [ "proteins" ], "offsets": [ [ 1014, 1022 ] ], "normalized": [] }, { "id": "3827", "type": "other_name", "text": [ "immunostaining" ], "offsets": [ [ 1050, 1064 ] ], "normalized": [] }, { "id": "3828", "type": "other_name", "text": [ "ELISA procedures" ], "offsets": [ [ 1082, 1098 ] ], "normalized": [] }, { "id": "3829", "type": "protein_molecule", "text": [ "vimentin" ], "offsets": [ [ 1115, 1123 ] ], "normalized": [] }, { "id": "3830", "type": "other_name", "text": [ "cell shape changes" ], "offsets": [ [ 1140, 1158 ] ], "normalized": [] }, { "id": "3831", "type": "(AND protein_molecule protein_molecule)", "text": [ "cytokeratins 8 and 18" ], "offsets": [ [ 1160, 1181 ] ], "normalized": [] }, { "id": "3832", "type": "", "text": [ "cytokeratins" ], "offsets": [ [ 1160, 1172 ] ], "normalized": [] }, { "id": "3833", "type": "", "text": [ "8" ], "offsets": [ [ 1173, 1174 ] ], "normalized": [] }, { "id": "3834", "type": "", "text": [ "18" ], "offsets": [ [ 1179, 1181 ] ], "normalized": [] }, { "id": "3835", "type": "cell_type", "text": [ "differentiated cell types" ], "offsets": [ [ 1199, 1224 ] ], "normalized": [] }, { "id": "3836", "type": "tissue", "text": [ "prostate epithelia" ], "offsets": [ [ 1228, 1246 ] ], "normalized": [] }, { "id": "3837", "type": "protein_molecule", "text": [ "neuron-specific enolase" ], "offsets": [ [ 1252, 1275 ] ], "normalized": [] }, { "id": "3838", "type": "other_organic_compound", "text": [ "serotonin" ], "offsets": [ [ 1280, 1289 ] ], "normalized": [] }, { "id": "3839", "type": "cell_type", "text": [ "neuroendocrine cells" ], "offsets": [ [ 1307, 1327 ] ], "normalized": [] }, { "id": "3840", "type": "other_name", "text": [ "cellular changes" ], "offsets": [ [ 1340, 1356 ] ], "normalized": [] }, { "id": "3841", "type": "other_name", "text": [ "cell growth" ], "offsets": [ [ 1380, 1391 ] ], "normalized": [] }, { "id": "3842", "type": "other_name", "text": [ "terminal differentiation" ], "offsets": [ [ 1430, 1454 ] ], "normalized": [] }, { "id": "3843", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 1466, 1473 ] ], "normalized": [] }, { "id": "3844", "type": "protein_family_or_group", "text": [ "growth modulator" ], "offsets": [ [ 1551, 1567 ] ], "normalized": [] }, { "id": "3845", "type": "protein_family_or_group", "text": [ "TGF" ], "offsets": [ [ 1692, 1695 ] ], "normalized": [] }, { "id": "3846", "type": "protein_family_or_group", "text": [ "TNF" ], "offsets": [ [ 1697, 1700 ] ], "normalized": [] }, { "id": "3847", "type": "protein_family_or_group", "text": [ "lymphokines" ], "offsets": [ [ 1726, 1737 ] ], "normalized": [] }, { "id": "3848", "type": "(AND cell_type cell_type)", "text": [ "lymphoid and prostatic cells" ], "offsets": [ [ 1763, 1791 ] ], "normalized": [] }, { "id": "3849", "type": "", "text": [ "lymphoid" ], "offsets": [ [ 1763, 1771 ] ], "normalized": [] }, { "id": "3850", "type": "", "text": [ "prostatic" ], "offsets": [ [ 1776, 1785 ] ], "normalized": [] }, { "id": "3851", "type": "", "text": [ "cells" ], "offsets": [ [ 1786, 1791 ] ], "normalized": [] } ]

[]

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[ { "id": "3853", "type": "title", "text": [ "Platelet-activating factor stimulates transcription of the heparin-binding epidermal growth factor-like growth factor in monocytes. Correlation with an increased kappa B binding activity." ], "offsets": [ [ 0, 187 ] ] }, { "id": "3854", "type": "abstract", "text": [ "Human peripheral blood monocytes responded to stimulation of platelet-activating factor (PAF) with up-regulation of the transcript for heparin-binding epidermal growth factor-like growth factor (HB-EGF), a potent mitogen for vascular smooth muscle cells. This function of PAF was observed at nanomolar concentrations of the ligand, starting at 30 min after stimulation. The PAF-induced up-regulation of HB-EGF mRNA was accompanied by an increase in kappa B binding activity. These functions of PAF appeared to be mediated through the cell surface PAF receptors, as two PAF receptor antagonists, WEB 2086 and L-659,989, blocked both the up-regulation of HB-EGF mRNA and kappa B binding activity induced by PAF. The antagonists, however, had no effect on phorbol ester-induced up-regulation of HB-EGF mRNA and kappa B binding activity. Pretreatment of monocytes with pertussis toxin inhibited these functions of PAF, whereas cholera toxin had no inhibitory effect. Pyrrolidine dithiocarbamate, an inhibitor for NF-kappa B activation, markedly reduced PAF-stimulated kappa B binding activity as well as up-regulation of HB-EGF mRNA. These results suggest a potential role of PAF in HB-EGF expression and provide evidence that this stimulation may occur through increased kappa B binding activity." ], "offsets": [ [ 188, 1481 ] ] } ]

[ { "id": "3855", "type": "protein_family_or_group", "text": [ "Platelet-activating factor" ], "offsets": [ [ 0, 26 ] ], "normalized": [] }, { "id": "3856", "type": "protein_molecule", "text": [ "heparin-binding epidermal growth factor-like growth factor" ], "offsets": [ [ 59, 117 ] ], "normalized": [] }, { "id": "3857", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 121, 130 ] ], "normalized": [] }, { "id": "3858", "type": "other_name", "text": [ "kappa B binding activity" ], "offsets": [ [ 162, 186 ] ], "normalized": [] }, { "id": "3859", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 211, 220 ] ], "normalized": [] }, { "id": "3860", "type": "protein_molecule", "text": [ "platelet-activating factor" ], "offsets": [ [ 249, 275 ] ], "normalized": [] }, { "id": "3861", "type": "protein_molecule", "text": [ "PAF" ], "offsets": [ [ 277, 280 ] ], "normalized": [] }, { "id": "3862", "type": "protein_molecule", "text": [ "heparin-binding epidermal growth factor-like growth factor" ], "offsets": [ [ 323, 381 ] ], "normalized": [] }, { "id": "3863", "type": "protein_molecule", "text": [ "HB-EGF" ], "offsets": [ [ 383, 389 ] ], "normalized": [] }, { "id": "3864", "type": "protein_family_or_group", "text": [ "potent mitogen" ], "offsets": [ [ 394, 408 ] ], "normalized": [] }, { "id": "3865", "type": "cell_type", "text": [ "vascular smooth muscle cells" ], "offsets": [ [ 413, 441 ] ], "normalized": [] }, { "id": "3866", "type": "protein_molecule", "text": [ "PAF" ], "offsets": [ [ 460, 463 ] ], "normalized": [] }, { "id": "3867", "type": "protein_molecule", "text": [ "PAF" ], "offsets": [ [ 562, 565 ] ], "normalized": [] }, { "id": "3868", "type": "RNA_molecule", "text": [ "HB-EGF mRNA" ], "offsets": [ [ 591, 602 ] ], "normalized": [] }, { "id": "3869", "type": "protein_molecule", "text": [ "HB-EGF" ], "offsets": [ [ 591, 597 ] ], "normalized": [] }, { "id": "3870", "type": "other_name", "text": [ "kappa B binding activity" ], "offsets": [ [ 637, 661 ] ], "normalized": [] }, { "id": "3871", "type": "protein_molecule", "text": [ "PAF" ], "offsets": [ [ 682, 685 ] ], "normalized": [] }, { "id": "3872", "type": "protein_family_or_group", "text": [ "cell surface PAF receptors" ], "offsets": [ [ 722, 748 ] ], "normalized": [] }, { "id": "3873", "type": "protein_molecule", "text": [ "PAF" ], "offsets": [ [ 735, 738 ] ], "normalized": [] }, { "id": "3874", "type": "other_name", "text": [ "PAF receptor antagonists" ], "offsets": [ [ 757, 781 ] ], "normalized": [] }, { "id": "3875", "type": "protein_molecule", "text": [ "PAF" ], "offsets": [ [ 757, 760 ] ], "normalized": [] }, { "id": "3876", "type": "other_organic_compound", "text": [ "WEB 2086" ], "offsets": [ [ 783, 791 ] ], "normalized": [] }, { "id": "3877", "type": "other_organic_compound", "text": [ "L-659,989" ], "offsets": [ [ 796, 805 ] ], "normalized": [] }, { "id": "3878", "type": "RNA_molecule", "text": [ "HB-EGF mRNA" ], "offsets": [ [ 841, 852 ] ], "normalized": [] }, { "id": "3879", "type": "protein_molecule", "text": [ "HB-EGF" ], "offsets": [ [ 841, 847 ] ], "normalized": [] }, { "id": "3880", "type": "other_name", "text": [ "kappa B binding activity" ], "offsets": [ [ 857, 881 ] ], "normalized": [] }, { "id": "3881", "type": "protein_molecule", "text": [ "PAF" ], "offsets": [ [ 893, 896 ] ], "normalized": [] }, { "id": "3882", "type": "other_name", "text": [ "phorbol ester-induced up-regulation" ], "offsets": [ [ 941, 976 ] ], "normalized": [] }, { "id": "3883", "type": "other_organic_compound", "text": [ "phorbol ester" ], "offsets": [ [ 941, 954 ] ], "normalized": [] }, { "id": "3884", "type": "RNA_family_or_group", "text": [ "HB-EGF mRNA" ], "offsets": [ [ 980, 991 ] ], "normalized": [] }, { "id": "3885", "type": "protein_molecule", "text": [ "HB-EGF" ], "offsets": [ [ 980, 986 ] ], "normalized": [] }, { "id": "3886", "type": "other_name", "text": [ "kappa B binding activity" ], "offsets": [ [ 996, 1020 ] ], "normalized": [] }, { "id": "3887", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 1038, 1047 ] ], "normalized": [] }, { "id": "3888", "type": "protein_molecule", "text": [ "PAF" ], "offsets": [ [ 1098, 1101 ] ], "normalized": [] }, { "id": "3889", "type": "other_organic_compound", "text": [ "cholera toxin" ], "offsets": [ [ 1111, 1124 ] ], "normalized": [] }, { "id": "3890", "type": "other_organic_compound", "text": [ "Pyrrolidine dithiocarbamate" ], "offsets": [ [ 1151, 1178 ] ], "normalized": [] }, { "id": "3891", "type": "other_name", "text": [ "NF-kappa B activation" ], "offsets": [ [ 1197, 1218 ] ], "normalized": [] }, { "id": "3892", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 1197, 1207 ] ], "normalized": [] }, { "id": "3893", "type": "other_name", "text": [ "PAF-stimulated kappa B binding activity" ], "offsets": [ [ 1237, 1276 ] ], "normalized": [] }, { "id": "3894", "type": "protein_molecule", "text": [ "PAF" ], "offsets": [ [ 1237, 1240 ] ], "normalized": [] }, { "id": "3895", "type": "other_name", "text": [ "kappa B binding activity" ], "offsets": [ [ 1252, 1276 ] ], "normalized": [] }, { "id": "3896", "type": "RNA_molecule", "text": [ "HB-EGF mRNA" ], "offsets": [ [ 1305, 1316 ] ], "normalized": [] }, { "id": "3897", "type": "protein_molecule", "text": [ "HB-EGF" ], "offsets": [ [ 1305, 1311 ] ], "normalized": [] }, { "id": "3898", "type": "protein_molecule", "text": [ "PAF" ], "offsets": [ [ 1360, 1363 ] ], "normalized": [] }, { "id": "3899", "type": "other_name", "text": [ "HB-EGF expression" ], "offsets": [ [ 1367, 1384 ] ], "normalized": [] }, { "id": "3900", "type": "protein_family_or_group", "text": [ "HB-EGF" ], "offsets": [ [ 1367, 1373 ] ], "normalized": [] }, { "id": "3901", "type": "protein_molecule", "text": [ "HB-EGF" ], "offsets": [ [ 1367, 1373 ] ], "normalized": [] }, { "id": "3902", "type": "other_name", "text": [ "kappa B binding activity" ], "offsets": [ [ 1456, 1480 ] ], "normalized": [] } ]

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[ { "id": "3904", "type": "title", "text": [ "Mapping of the interaction site of the defective transcription factor in the class II major histocompatibility complex mutant cell line clone-13 to the divergent X2-box." ], "offsets": [ [ 0, 169 ] ] }, { "id": "3905", "type": "abstract", "text": [ "We have previously described a mutant B lymphoblastoid cell line, Clone-13, that expresses HLA-DQ in the absence of HLA-DR and -DP. Several criteria indicated that the defect in this cell line influences the activity of an isotype-specific transcription factor. Indeed, transient transfection of HLA-DRA and DQB reporter constructs indicated that the affected factor operates via cis-elements located between -141 base pairs and the transcription initiation site. A series of hybrid DRA/DQB reporter constructs was generated to further map the relevant cis-elements in this system. Insertion of oligonucleotides spanning the DQB X-box (but not the DQB-W region or the DQB Y-box) upstream of -141 in a DRA reporter plasmid rescued expression to nearly wild-type levels. Substitution promoters were then generated where the entire X-box, or only the X1- or X2-boxes of HLA-DRA were replaced with the analogous regions of HLA-DQB. The DQB X2-box was able to restore expression to the silent DRA reporter construct. Moreover, replacement of the DQB X2-box with the DRA X2-box markedly diminished the activity of the DQB promoter in the mutant cell. None of the hybrid reporter constructs were defective when transfected into the wild-type, HLA-DR/-DQ positive parental cell line, Jijoye. These studies suggest that the divergent X2-box of the class II major histocompatibility complex promoters plays an important role in influencing differential expression of the human class II isotypes." ], "offsets": [ [ 170, 1655 ] ] } ]

[ { "id": "3906", "type": "protein_domain_or_region", "text": [ "interaction site" ], "offsets": [ [ 15, 31 ] ], "normalized": [] }, { "id": "3907", "type": "protein_family_or_group", "text": [ "defective transcription factor" ], "offsets": [ [ 39, 69 ] ], "normalized": [] }, { "id": "3908", "type": "protein_family_or_group", "text": [ "transcription factor" ], "offsets": [ [ 49, 69 ] ], "normalized": [] }, { "id": "3909", "type": "cell_line", "text": [ "class II major histocompatibility complex mutant cell line clone-13" ], "offsets": [ [ 77, 144 ] ], "normalized": [] }, { "id": "3910", "type": "DNA_domain_or_region", "text": [ "divergent X2-box" ], "offsets": [ [ 152, 168 ] ], "normalized": [] }, { "id": "3911", "type": "cell_line", "text": [ "mutant B lymphoblastoid cell line" ], "offsets": [ [ 201, 234 ] ], "normalized": [] }, { "id": "3912", "type": "cell_line", "text": [ "Clone-13," ], "offsets": [ [ 236, 245 ] ], "normalized": [] }, { "id": "3913", "type": "protein_molecule", "text": [ "HLA-DQ" ], "offsets": [ [ 261, 267 ] ], "normalized": [] }, { "id": "3914", "type": "(AND protein_molecule protein_molecule)", "text": [ "HLA-DR and -DP" ], "offsets": [ [ 286, 300 ] ], "normalized": [] }, { "id": "3915", "type": "", "text": [ "HLA" ], "offsets": [ [ 261, 264 ] ], "normalized": [] }, { "id": "3916", "type": "", "text": [ "-DR" ], "offsets": [ [ 289, 292 ] ], "normalized": [] }, { "id": "3917", "type": "", "text": [ "-DP" ], "offsets": [ [ 297, 300 ] ], "normalized": [] }, { "id": "3918", "type": "protein_family_or_group", "text": [ "isotype-specific transcription factor" ], "offsets": [ [ 393, 430 ] ], "normalized": [] }, { "id": "3919", "type": "(AND DNA_molecule DNA_molecule)", "text": [ "HLA-DRA and DQB reporter constructs" ], "offsets": [ [ 466, 501 ] ], "normalized": [] }, { "id": "3920", "type": "", "text": [ "HLA-DRA" ], "offsets": [ [ 466, 473 ] ], "normalized": [] }, { "id": "3921", "type": "", "text": [ "DQB" ], "offsets": [ [ 478, 481 ] ], "normalized": [] }, { "id": "3922", "type": "", "text": [ "reporter constructs" ], "offsets": [ [ 482, 501 ] ], "normalized": [] }, { "id": "3923", "type": "DNA_family_or_group", "text": [ "cis-elements" ], "offsets": [ [ 550, 562 ] ], "normalized": [] }, { "id": "3924", "type": "DNA_domain_or_region", "text": [ "-141 base pairs" ], "offsets": [ [ 579, 594 ] ], "normalized": [] }, { "id": "3925", "type": "DNA_domain_or_region", "text": [ "transcription initiation site" ], "offsets": [ [ 603, 632 ] ], "normalized": [] }, { "id": "3926", "type": "DNA_family_or_group", "text": [ "hybrid DRA/DQB reporter constructs" ], "offsets": [ [ 646, 680 ] ], "normalized": [] }, { "id": "3927", "type": "DNA_family_or_group", "text": [ "reporter constructs" ], "offsets": [ [ 661, 680 ] ], "normalized": [] }, { "id": "3928", "type": "DNA_family_or_group", "text": [ "cis-elements" ], "offsets": [ [ 723, 735 ] ], "normalized": [] }, { "id": "3929", "type": "polynucleotide", "text": [ "oligonucleotides" ], "offsets": [ [ 765, 781 ] ], "normalized": [] }, { "id": "3930", "type": "DNA_domain_or_region", "text": [ "DQB X-box" ], "offsets": [ [ 795, 804 ] ], "normalized": [] }, { "id": "3931", "type": "DNA_domain_or_region", "text": [ "DQB-W region" ], "offsets": [ [ 818, 830 ] ], "normalized": [] }, { "id": "3932", "type": "DNA_domain_or_region", "text": [ "DQB Y-box" ], "offsets": [ [ 838, 847 ] ], "normalized": [] }, { "id": "3933", "type": "DNA_domain_or_region", "text": [ "upstream of -141" ], "offsets": [ [ 849, 865 ] ], "normalized": [] }, { "id": "3934", "type": "DNA_molecule", "text": [ "DRA reporter plasmid" ], "offsets": [ [ 871, 891 ] ], "normalized": [] }, { "id": "3935", "type": "other_name", "text": [ "wild-type levels" ], "offsets": [ [ 921, 937 ] ], "normalized": [] }, { "id": "3936", "type": "DNA_domain_or_region", "text": [ "X-box" ], "offsets": [ [ 999, 1004 ] ], "normalized": [] }, { "id": "3937", "type": "(OR DNA_domain_or_region DNA_domain_or_region)", "text": [ "X1- or X2-boxes" ], "offsets": [ [ 1018, 1033 ] ], "normalized": [] }, { "id": "3938", "type": "", "text": [ "X1-" ], "offsets": [ [ 1018, 1021 ] ], "normalized": [] }, { "id": "3939", "type": "", "text": [ "X2-" ], "offsets": [ [ 1025, 1028 ] ], "normalized": [] }, { "id": "3940", "type": "", "text": [ "boxes" ], "offsets": [ [ 1028, 1033 ] ], "normalized": [] }, { "id": "3941", "type": "DNA_domain_or_region", "text": [ "HLA-DRA" ], "offsets": [ [ 1037, 1044 ] ], "normalized": [] }, { "id": "3942", "type": "DNA_domain_or_region", "text": [ "HLA-DQB" ], "offsets": [ [ 1089, 1096 ] ], "normalized": [] }, { "id": "3943", "type": "DNA_domain_or_region", "text": [ "DQB X2-box" ], "offsets": [ [ 1102, 1112 ] ], "normalized": [] }, { "id": "3944", "type": "DNA_molecule", "text": [ "silent DRA reporter construct" ], "offsets": [ [ 1151, 1180 ] ], "normalized": [] }, { "id": "3945", "type": "DNA_domain_or_region", "text": [ "DQB X2-box" ], "offsets": [ [ 1211, 1221 ] ], "normalized": [] }, { "id": "3946", "type": "DNA_domain_or_region", "text": [ "DRA X2-box" ], "offsets": [ [ 1231, 1241 ] ], "normalized": [] }, { "id": "3947", "type": "DNA_domain_or_region", "text": [ "DQB promoter" ], "offsets": [ [ 1282, 1294 ] ], "normalized": [] }, { "id": "3948", "type": "cell_line", "text": [ "mutant cell" ], "offsets": [ [ 1302, 1313 ] ], "normalized": [] }, { "id": "3949", "type": "DNA_family_or_group", "text": [ "hybrid reporter constructs" ], "offsets": [ [ 1327, 1353 ] ], "normalized": [] }, { "id": "3950", "type": "DNA_family_or_group", "text": [ "reporter constructs" ], "offsets": [ [ 1334, 1353 ] ], "normalized": [] }, { "id": "3951", "type": "protein_family_or_group", "text": [ "wild-type" ], "offsets": [ [ 1395, 1404 ] ], "normalized": [] }, { "id": "3952", "type": "cell_line", "text": [ "HLA-DR/-DQ positive parental cell line" ], "offsets": [ [ 1406, 1444 ] ], "normalized": [] }, { "id": "3953", "type": "cell_line", "text": [ "Jijoye" ], "offsets": [ [ 1446, 1452 ] ], "normalized": [] }, { "id": "3954", "type": "DNA_domain_or_region", "text": [ "divergent X2-box" ], "offsets": [ [ 1485, 1501 ] ], "normalized": [] }, { "id": "3955", "type": "DNA_family_or_group", "text": [ "class II major histocompatibility complex promoters" ], "offsets": [ [ 1509, 1560 ] ], "normalized": [] }, { "id": "3956", "type": "protein_complex", "text": [ "class II major histocompatibility complex" ], "offsets": [ [ 1509, 1550 ] ], "normalized": [] }, { "id": "3957", "type": "other_name", "text": [ "differential expression" ], "offsets": [ [ 1600, 1623 ] ], "normalized": [] }, { "id": "3958", "type": "DNA_family_or_group", "text": [ "human class II isotypes" ], "offsets": [ [ 1631, 1654 ] ], "normalized": [] } ]

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[]

[ { "id": "3960", "type": "title", "text": [ "Restoration of the Epstein-Barr virus ZEBRA protein's capacity to disrupt latency by the addition of heterologous activation regions." ], "offsets": [ [ 0, 133 ] ] }, { "id": "3961", "type": "abstract", "text": [ "The ZEBRA protein has a unique biological function among herpesviral proteins. It is responsible for the disruption of Epstein-Barr virus (EBV) latency and the induction of the lytic cycle. ZEBRA is a bZIP transcriptional activator which binds as a dimer to 7-bp response elements within EBV promoters and is directly involved in the stimulation of virus replication at the EBV lytic origin. We have employed the ZEBRA/EBV biological system to test whether a heterologous activation domain can substitute for another activation domain (the ZEBRA domain). The ZEBRA activation region was replaced with the potent acid activation region from the herpes simplex virus VP16 protein or with the activation region of the EBV R protein. Both chimeras were found to transactivate model and native promoters at equivalent or better levels than ZEBRA itself. Activation was not target- or cell-type dependent, nor was it dependent on the presence of virus. These activation domains restored ZEBRA's ability to induce early antigen and to stimulate origin replication to levels that were equal to or greater than those of wild type. These studies suggest that the specificities of some of the known biological functions of ZEBRA are not dependent upon the nature of the activation domain present within ZEBRA." ], "offsets": [ [ 134, 1432 ] ] } ]

[ { "id": "3962", "type": "protein_molecule", "text": [ "Epstein-Barr virus ZEBRA protein" ], "offsets": [ [ 19, 51 ] ], "normalized": [] }, { "id": "3963", "type": "virus", "text": [ "Epstein-Barr virus" ], "offsets": [ [ 19, 37 ] ], "normalized": [] }, { "id": "3964", "type": "protein_domain_or_region", "text": [ "heterologous activation regions" ], "offsets": [ [ 101, 132 ] ], "normalized": [] }, { "id": "3965", "type": "protein_molecule", "text": [ "ZEBRA protein" ], "offsets": [ [ 138, 151 ] ], "normalized": [] }, { "id": "3966", "type": "protein_family_or_group", "text": [ "herpesviral proteins" ], "offsets": [ [ 191, 211 ] ], "normalized": [] }, { "id": "3967", "type": "other_name", "text": [ "Epstein-Barr virus (EBV) latency" ], "offsets": [ [ 253, 285 ] ], "normalized": [] }, { "id": "3968", "type": "virus", "text": [ "Epstein-Barr virus" ], "offsets": [ [ 253, 271 ] ], "normalized": [] }, { "id": "3969", "type": "virus", "text": [ "EBV" ], "offsets": [ [ 273, 276 ] ], "normalized": [] }, { "id": "3970", "type": "other_name", "text": [ "lytic cycle" ], "offsets": [ [ 311, 322 ] ], "normalized": [] }, { "id": "3971", "type": "protein_molecule", "text": [ "ZEBRA" ], "offsets": [ [ 324, 329 ] ], "normalized": [] }, { "id": "3972", "type": "protein_family_or_group", "text": [ "bZIP transcriptional activator" ], "offsets": [ [ 335, 365 ] ], "normalized": [] }, { "id": "3973", "type": "DNA_family_or_group", "text": [ "7-bp response elements" ], "offsets": [ [ 392, 414 ] ], "normalized": [] }, { "id": "3974", "type": "DNA_domain_or_region", "text": [ "EBV promoters" ], "offsets": [ [ 422, 435 ] ], "normalized": [] }, { "id": "3975", "type": "other_name", "text": [ "virus replication" ], "offsets": [ [ 483, 500 ] ], "normalized": [] }, { "id": "3976", "type": "DNA_domain_or_region", "text": [ "EBV lytic origin" ], "offsets": [ [ 508, 524 ] ], "normalized": [] }, { "id": "3977", "type": "other_name", "text": [ "ZEBRA/EBV biological system" ], "offsets": [ [ 547, 574 ] ], "normalized": [] }, { "id": "3978", "type": "protein_molecule", "text": [ "ZEBRA" ], "offsets": [ [ 547, 552 ] ], "normalized": [] }, { "id": "3979", "type": "protein_domain_or_region", "text": [ "heterologous activation domain" ], "offsets": [ [ 593, 623 ] ], "normalized": [] }, { "id": "3980", "type": "protein_domain_or_region", "text": [ "ZEBRA domain" ], "offsets": [ [ 674, 686 ] ], "normalized": [] }, { "id": "3981", "type": "protein_molecule", "text": [ "ZEBRA" ], "offsets": [ [ 674, 679 ] ], "normalized": [] }, { "id": "3982", "type": "protein_domain_or_region", "text": [ "ZEBRA activation region" ], "offsets": [ [ 693, 716 ] ], "normalized": [] }, { "id": "3983", "type": "protein_molecule", "text": [ "ZEBRA" ], "offsets": [ [ 693, 698 ] ], "normalized": [] }, { "id": "3984", "type": "protein_domain_or_region", "text": [ "acid activation region" ], "offsets": [ [ 746, 768 ] ], "normalized": [] }, { "id": "3985", "type": "protein_molecule", "text": [ "herpes simplex virus VP16 protein" ], "offsets": [ [ 778, 811 ] ], "normalized": [] }, { "id": "3986", "type": "virus", "text": [ "herpes simplex virus" ], "offsets": [ [ 778, 798 ] ], "normalized": [] }, { "id": "3987", "type": "protein_domain_or_region", "text": [ "activation region" ], "offsets": [ [ 699, 716 ] ], "normalized": [] }, { "id": "3988", "type": "protein_molecule", "text": [ "EBV R protein" ], "offsets": [ [ 849, 862 ] ], "normalized": [] }, { "id": "3989", "type": "protein_molecule", "text": [ "ZEBRA" ], "offsets": [ [ 969, 974 ] ], "normalized": [] }, { "id": "3990", "type": "virus", "text": [ "virus" ], "offsets": [ [ 1074, 1079 ] ], "normalized": [] }, { "id": "3991", "type": "protein_molecule", "text": [ "ZEBRA" ], "offsets": [ [ 1115, 1120 ] ], "normalized": [] }, { "id": "3992", "type": "protein_family_or_group", "text": [ "early antigen" ], "offsets": [ [ 1141, 1154 ] ], "normalized": [] }, { "id": "3993", "type": "other_name", "text": [ "origin replication" ], "offsets": [ [ 1172, 1190 ] ], "normalized": [] }, { "id": "3994", "type": "protein_molecule", "text": [ "ZEBRA" ], "offsets": [ [ 1346, 1351 ] ], "normalized": [] }, { "id": "3995", "type": "protein_domain_or_region", "text": [ "activation domain present" ], "offsets": [ [ 1393, 1418 ] ], "normalized": [] }, { "id": "3996", "type": "protein_molecule", "text": [ "ZEBRA" ], "offsets": [ [ 1426, 1431 ] ], "normalized": [] } ]

[]

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[ { "id": "3998", "type": "title", "text": [ "Interleukin 4 activates a signal transducer and activator of transcription (Stat) protein which interacts with an interferon-gamma activation site-like sequence upstream of the I epsilon exon in a human B cell line. Evidence for the involvement of Janus kinase 3 and interleukin-4 Stat." ], "offsets": [ [ 0, 286 ] ] }, { "id": "3999", "type": "abstract", "text": [ "Germ line C transcripts can be induced by IL-4 in the human B cell line, BL-2. Utilizing a IFN-gamma activation site-like DNA sequence element located upstream of the I epsilon exon, we demonstrated by gel mobility shift assays that IL-4 induced a binding activity in the cytosol and nucleus of BL-2 cells. This factor was designated IL-4 NAF (IL-4-induced nuclear-activating factors) and was identified as a tyrosine phosphoprotein, which translocates from the cytosol to the nucleus upon IL-4 treatment. Because these are the characteristics of a signal transducer and activator of transcription (Stat) protein, we determined whether antibodies to Stat proteins will interfere with gel mobility shift and found that antibodies to IL-4 Stat, also known as Stat6, but not antibodies to other Stat proteins, interfere with the formation of the IL-4 NAF complex. Congruous with the involvement of a Stat protein, IL-4 induced robust Janus kinase 3 (JAK3) activity in BL-2 cells. Cotransfection of JAK3 with IL-4 Stat into COS-7 cells produced an intracellular activity which bound the same IFN-gamma activation site-like sequence and comigrated with IL-4 NAF in electrophoretic mobility shift assay. These results show that IL-4 NAF is IL-4 Stat, which is activated by JAK3 in response to IL-4 receptor engagement." ], "offsets": [ [ 287, 1599 ] ] } ]

[ { "id": "4000", "type": "protein_molecule", "text": [ "Interleukin 4" ], "offsets": [ [ 0, 13 ] ], "normalized": [] }, { "id": "4001", "type": "other_name", "text": [ "signal transducer" ], "offsets": [ [ 26, 43 ] ], "normalized": [] }, { "id": "4002", "type": "other_name", "text": [ "activator" ], "offsets": [ [ 48, 57 ] ], "normalized": [] }, { "id": "4003", "type": "protein_family_or_group", "text": [ "transcription (Stat) protein" ], "offsets": [ [ 61, 89 ] ], "normalized": [] }, { "id": "4004", "type": "DNA_domain_or_region", "text": [ "interferon-gamma activation site-like sequence" ], "offsets": [ [ 114, 160 ] ], "normalized": [] }, { "id": "4005", "type": "DNA_domain_or_region", "text": [ "I epsilon exon" ], "offsets": [ [ 177, 191 ] ], "normalized": [] }, { "id": "4006", "type": "cell_line", "text": [ "human B cell line" ], "offsets": [ [ 197, 214 ] ], "normalized": [] }, { "id": "4007", "type": "protein_molecule", "text": [ "Janus kinase 3" ], "offsets": [ [ 248, 262 ] ], "normalized": [] }, { "id": "4008", "type": "protein_molecule", "text": [ "interleukin-4 Stat" ], "offsets": [ [ 267, 285 ] ], "normalized": [] }, { "id": "4009", "type": "RNA_family_or_group", "text": [ "Germ line C transcripts" ], "offsets": [ [ 287, 310 ] ], "normalized": [] }, { "id": "4010", "type": "protein_molecule", "text": [ "IL-4" ], "offsets": [ [ 329, 333 ] ], "normalized": [] }, { "id": "4011", "type": "cell_line", "text": [ "human B cell line" ], "offsets": [ [ 341, 358 ] ], "normalized": [] }, { "id": "4012", "type": "cell_line", "text": [ "BL-2" ], "offsets": [ [ 360, 364 ] ], "normalized": [] }, { "id": "4013", "type": "DNA_domain_or_region", "text": [ "IFN-gamma activation site-like DNA sequence element" ], "offsets": [ [ 378, 429 ] ], "normalized": [] }, { "id": "4014", "type": "DNA_domain_or_region", "text": [ "I epsilon exon" ], "offsets": [ [ 454, 468 ] ], "normalized": [] }, { "id": "4015", "type": "other_name", "text": [ "gel mobility shift assays" ], "offsets": [ [ 489, 514 ] ], "normalized": [] }, { "id": "4016", "type": "protein_molecule", "text": [ "IL-4" ], "offsets": [ [ 520, 524 ] ], "normalized": [] }, { "id": "4017", "type": "cell_component", "text": [ "cytosol" ], "offsets": [ [ 559, 566 ] ], "normalized": [] }, { "id": "4018", "type": "cell_component", "text": [ "nucleus" ], "offsets": [ [ 571, 578 ] ], "normalized": [] }, { "id": "4019", "type": "cell_line", "text": [ "BL-2 cells" ], "offsets": [ [ 582, 592 ] ], "normalized": [] }, { "id": "4020", "type": "protein_molecule", "text": [ "IL-4 NAF" ], "offsets": [ [ 621, 629 ] ], "normalized": [] }, { "id": "4021", "type": "protein_molecule", "text": [ "IL-4" ], "offsets": [ [ 621, 625 ] ], "normalized": [] }, { "id": "4022", "type": "protein_molecule", "text": [ "IL-4-induced nuclear-activating factors" ], "offsets": [ [ 631, 670 ] ], "normalized": [] }, { "id": "4023", "type": "protein_molecule", "text": [ "IL-4" ], "offsets": [ [ 631, 635 ] ], "normalized": [] }, { "id": "4024", "type": "protein_family_or_group", "text": [ "tyrosine phosphoprotein" ], "offsets": [ [ 696, 719 ] ], "normalized": [] }, { "id": "4025", "type": "cell_component", "text": [ "cytosol" ], "offsets": [ [ 749, 756 ] ], "normalized": [] }, { "id": "4026", "type": "cell_component", "text": [ "nucleus" ], "offsets": [ [ 764, 771 ] ], "normalized": [] }, { "id": "4027", "type": "other_name", "text": [ "IL-4 treatment" ], "offsets": [ [ 777, 791 ] ], "normalized": [] }, { "id": "4028", "type": "protein_molecule", "text": [ "IL-4" ], "offsets": [ [ 777, 781 ] ], "normalized": [] }, { "id": "4029", "type": "protein_family_or_group", "text": [ "signal transducer and activator of transcription (Stat) protein" ], "offsets": [ [ 836, 899 ] ], "normalized": [] }, { "id": "4030", "type": "protein_family_or_group", "text": [ "antibodies to Stat proteins" ], "offsets": [ [ 923, 950 ] ], "normalized": [] }, { "id": "4031", "type": "other_name", "text": [ "gel mobility shift" ], "offsets": [ [ 971, 989 ] ], "normalized": [] }, { "id": "4032", "type": "protein_family_or_group", "text": [ "antibodies to IL-4 Stat" ], "offsets": [ [ 1005, 1028 ] ], "normalized": [] }, { "id": "4033", "type": "protein_molecule", "text": [ "IL-4 Stat" ], "offsets": [ [ 1019, 1028 ] ], "normalized": [] }, { "id": "4034", "type": "protein_molecule", "text": [ "IL-4" ], "offsets": [ [ 1019, 1023 ] ], "normalized": [] }, { "id": "4035", "type": "protein_molecule", "text": [ "Stat6" ], "offsets": [ [ 1044, 1049 ] ], "normalized": [] }, { "id": "4036", "type": "protein_family_or_group", "text": [ "antibodies" ], "offsets": [ [ 923, 933 ] ], "normalized": [] }, { "id": "4037", "type": "protein_family_or_group", "text": [ "Stat proteins" ], "offsets": [ [ 937, 950 ] ], "normalized": [] }, { "id": "4038", "type": "protein_complex", "text": [ "IL-4 NAF complex" ], "offsets": [ [ 1130, 1146 ] ], "normalized": [] }, { "id": "4039", "type": "protein_molecule", "text": [ "IL-4" ], "offsets": [ [ 1130, 1134 ] ], "normalized": [] }, { "id": "4040", "type": "protein_family_or_group", "text": [ "Stat protein" ], "offsets": [ [ 1184, 1196 ] ], "normalized": [] }, { "id": "4041", "type": "protein_molecule", "text": [ "IL-4" ], "offsets": [ [ 1198, 1202 ] ], "normalized": [] }, { "id": "4042", "type": "other_name", "text": [ "Janus kinase 3 (JAK3) activity" ], "offsets": [ [ 1218, 1248 ] ], "normalized": [] }, { "id": "4043", "type": "protein_molecule", "text": [ "Janus kinase 3" ], "offsets": [ [ 1218, 1232 ] ], "normalized": [] }, { "id": "4044", "type": "protein_molecule", "text": [ "JAK3" ], "offsets": [ [ 1234, 1238 ] ], "normalized": [] }, { "id": "4045", "type": "cell_line", "text": [ "BL-2 cells" ], "offsets": [ [ 1252, 1262 ] ], "normalized": [] }, { "id": "4046", "type": "protein_molecule", "text": [ "JAK3" ], "offsets": [ [ 1282, 1286 ] ], "normalized": [] }, { "id": "4047", "type": "protein_molecule", "text": [ "IL-4 Stat" ], "offsets": [ [ 1292, 1301 ] ], "normalized": [] }, { "id": "4048", "type": "protein_molecule", "text": [ "IL-4" ], "offsets": [ [ 1292, 1296 ] ], "normalized": [] }, { "id": "4049", "type": "cell_line", "text": [ "COS-7 cells" ], "offsets": [ [ 1307, 1318 ] ], "normalized": [] }, { "id": "4050", "type": "DNA_domain_or_region", "text": [ "IFN-gamma activation site-like sequence" ], "offsets": [ [ 1375, 1414 ] ], "normalized": [] }, { "id": "4051", "type": "protein_complex", "text": [ "IL-4 NAF" ], "offsets": [ [ 1435, 1443 ] ], "normalized": [] }, { "id": "4052", "type": "protein_molecule", "text": [ "IL-4" ], "offsets": [ [ 1435, 1439 ] ], "normalized": [] }, { "id": "4053", "type": "other_name", "text": [ "electrophoretic mobility shift assay" ], "offsets": [ [ 1447, 1483 ] ], "normalized": [] }, { "id": "4054", "type": "protein_complex", "text": [ "IL-4 NAF" ], "offsets": [ [ 1509, 1517 ] ], "normalized": [] }, { "id": "4055", "type": "protein_molecule", "text": [ "IL-4" ], "offsets": [ [ 1509, 1513 ] ], "normalized": [] }, { "id": "4056", "type": "protein_molecule", "text": [ "IL-4 Stat" ], "offsets": [ [ 1521, 1530 ] ], "normalized": [] }, { "id": "4057", "type": "protein_molecule", "text": [ "IL-4" ], "offsets": [ [ 1521, 1525 ] ], "normalized": [] }, { "id": "4058", "type": "protein_molecule", "text": [ "JAK3" ], "offsets": [ [ 1554, 1558 ] ], "normalized": [] }, { "id": "4059", "type": "other_name", "text": [ "IL-4 receptor engagement" ], "offsets": [ [ 1574, 1598 ] ], "normalized": [] }, { "id": "4060", "type": "protein_molecule", "text": [ "IL-4" ], "offsets": [ [ 1574, 1578 ] ], "normalized": [] } ]

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[ { "id": "4062", "type": "title", "text": [ "Does activation of the TAL1 gene occur in a majority of patients with T-cell acute lymphoblastic leukemia? A pediatric oncology group study." ], "offsets": [ [ 0, 140 ] ] }, { "id": "4063", "type": "abstract", "text": [ "Almost 25% of patients with T-cell acute lymphoblastic leukemia (T-ALL) have tumor-specific rearrangements of the TAL1 gene. Although TAL1 expression has not been observed in normal lymphocytes, TAL1 gene products are readily detected in leukemic cells that harbor a rearranged TAL1 allele. Hence, it has been proposed that ectopic expression of TAL1 promotes the development of T-ALL. In this report, we show that TAL1 is expressed in the leukemic cells of most patients with T-ALL, including many that do not display an apparent TAL1 gene alteration. A polymorphic dinucleotide repeat in the transcribed sequences of TAL1 was used to determine the allele specificity of TAL1 transcription in primary T-ALL cells. Monoallelic expression of TAL1 was observed in the leukemic cells of all patients (8 of 8) bearing a TAL1 gene rearrangement. In the leukemic cells of patients without detectable TAL1 rearrangements, TAL1 transcription occurred in either a monoallelic (3 of 7 patients) or a biallelic (4 of 7 patients) fashion. Thus, TAL1 activation in these patients may result from subtle alterations in cis-acting regulatory sequences (affecting expression of a single TAL1 allele) or changes in trans-acting factors that control TAL1 transcription (affecting expression of both TAL1 alleles)." ], "offsets": [ [ 141, 1436 ] ] } ]

[ { "id": "4064", "type": "DNA_domain_or_region", "text": [ "TAL1 gene" ], "offsets": [ [ 23, 32 ] ], "normalized": [] }, { "id": "4065", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 56, 64 ] ], "normalized": [] }, { "id": "4066", "type": "other_name", "text": [ "T-cell acute lymphoblastic leukemia" ], "offsets": [ [ 70, 105 ] ], "normalized": [] }, { "id": "4067", "type": "other_name", "text": [ "pediatric oncology group study" ], "offsets": [ [ 109, 139 ] ], "normalized": [] }, { "id": "4068", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 155, 163 ] ], "normalized": [] }, { "id": "4069", "type": "other_name", "text": [ "T-cell acute lymphoblastic leukemia" ], "offsets": [ [ 169, 204 ] ], "normalized": [] }, { "id": "4070", "type": "other_name", "text": [ "T-ALL" ], "offsets": [ [ 206, 211 ] ], "normalized": [] }, { "id": "4071", "type": "other_name", "text": [ "tumor-specific rearrangements" ], "offsets": [ [ 218, 247 ] ], "normalized": [] }, { "id": "4072", "type": "DNA_domain_or_region", "text": [ "TAL1 gene" ], "offsets": [ [ 255, 264 ] ], "normalized": [] }, { "id": "4073", "type": "other_name", "text": [ "TAL1 expression" ], "offsets": [ [ 275, 290 ] ], "normalized": [] }, { "id": "4074", "type": "protein_molecule", "text": [ "TAL1" ], "offsets": [ [ 275, 279 ] ], "normalized": [] }, { "id": "4075", "type": "cell_type", "text": [ "normal lymphocytes" ], "offsets": [ [ 316, 334 ] ], "normalized": [] }, { "id": "4076", "type": "protein_family_or_group", "text": [ "TAL1 gene products" ], "offsets": [ [ 336, 354 ] ], "normalized": [] }, { "id": "4077", "type": "DNA_domain_or_region", "text": [ "TAL1 gene" ], "offsets": [ [ 336, 345 ] ], "normalized": [] }, { "id": "4078", "type": "cell_type", "text": [ "leukemic cells" ], "offsets": [ [ 379, 393 ] ], "normalized": [] }, { "id": "4079", "type": "DNA_family_or_group", "text": [ "rearranged TAL1 allele" ], "offsets": [ [ 408, 430 ] ], "normalized": [] }, { "id": "4080", "type": "other_name", "text": [ "ectopic expression" ], "offsets": [ [ 465, 483 ] ], "normalized": [] }, { "id": "4081", "type": "protein_molecule", "text": [ "TAL1" ], "offsets": [ [ 487, 491 ] ], "normalized": [] }, { "id": "4082", "type": "other_name", "text": [ "T-ALL" ], "offsets": [ [ 520, 525 ] ], "normalized": [] }, { "id": "4083", "type": "protein_molecule", "text": [ "TAL1" ], "offsets": [ [ 556, 560 ] ], "normalized": [] }, { "id": "4084", "type": "cell_type", "text": [ "leukemic cells" ], "offsets": [ [ 581, 595 ] ], "normalized": [] }, { "id": "4085", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 604, 612 ] ], "normalized": [] }, { "id": "4086", "type": "other_name", "text": [ "T-ALL" ], "offsets": [ [ 618, 623 ] ], "normalized": [] }, { "id": "4087", "type": "DNA_domain_or_region", "text": [ "TAL1 gene" ], "offsets": [ [ 672, 681 ] ], "normalized": [] }, { "id": "4088", "type": "protein_molecule", "text": [ "TAL1" ], "offsets": [ [ 672, 676 ] ], "normalized": [] }, { "id": "4089", "type": "protein_molecule", "text": [ "TAL1" ], "offsets": [ [ 760, 764 ] ], "normalized": [] }, { "id": "4090", "type": "other_name", "text": [ "allele specificity" ], "offsets": [ [ 791, 809 ] ], "normalized": [] }, { "id": "4091", "type": "protein_molecule", "text": [ "TAL1" ], "offsets": [ [ 813, 817 ] ], "normalized": [] }, { "id": "4092", "type": "cell_type", "text": [ "primary T-ALL cells" ], "offsets": [ [ 835, 854 ] ], "normalized": [] }, { "id": "4093", "type": "other_name", "text": [ "T-ALL" ], "offsets": [ [ 843, 848 ] ], "normalized": [] }, { "id": "4094", "type": "other_name", "text": [ "Monoallelic expression" ], "offsets": [ [ 856, 878 ] ], "normalized": [] }, { "id": "4095", "type": "protein_molecule", "text": [ "TAL1" ], "offsets": [ [ 882, 886 ] ], "normalized": [] }, { "id": "4096", "type": "cell_type", "text": [ "leukemic cells" ], "offsets": [ [ 907, 921 ] ], "normalized": [] }, { "id": "4097", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 929, 937 ] ], "normalized": [] }, { "id": "4098", "type": "other_name", "text": [ "TAL1 gene rearrangement" ], "offsets": [ [ 957, 980 ] ], "normalized": [] }, { "id": "4099", "type": "DNA_domain_or_region", "text": [ "TAL1 gene" ], "offsets": [ [ 957, 966 ] ], "normalized": [] }, { "id": "4100", "type": "protein_molecule", "text": [ "TAL1" ], "offsets": [ [ 957, 961 ] ], "normalized": [] }, { "id": "4101", "type": "cell_type", "text": [ "leukemic cells" ], "offsets": [ [ 989, 1003 ] ], "normalized": [] }, { "id": "4102", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 1007, 1015 ] ], "normalized": [] }, { "id": "4103", "type": "other_name", "text": [ "TAL1 rearrangements" ], "offsets": [ [ 1035, 1054 ] ], "normalized": [] }, { "id": "4104", "type": "protein_molecule", "text": [ "TAL1" ], "offsets": [ [ 1035, 1039 ] ], "normalized": [] }, { "id": "4105", "type": "other_name", "text": [ "TAL1 transcription" ], "offsets": [ [ 1056, 1074 ] ], "normalized": [] }, { "id": "4106", "type": "protein_molecule", "text": [ "TAL1" ], "offsets": [ [ 1056, 1060 ] ], "normalized": [] }, { "id": "4107", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 1116, 1124 ] ], "normalized": [] }, { "id": "4108", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 1149, 1157 ] ], "normalized": [] }, { "id": "4109", "type": "protein_molecule", "text": [ "TAL1" ], "offsets": [ [ 1174, 1178 ] ], "normalized": [] }, { "id": "4110", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 1199, 1207 ] ], "normalized": [] }, { "id": "4111", "type": "DNA_family_or_group", "text": [ "cis-acting regulatory sequences" ], "offsets": [ [ 1246, 1277 ] ], "normalized": [] }, { "id": "4112", "type": "DNA_domain_or_region", "text": [ "single TAL1 allele" ], "offsets": [ [ 1305, 1323 ] ], "normalized": [] }, { "id": "4113", "type": "protein_molecule", "text": [ "TAL1" ], "offsets": [ [ 1312, 1316 ] ], "normalized": [] }, { "id": "4114", "type": "other_name", "text": [ "TAL1 transcription" ], "offsets": [ [ 1373, 1391 ] ], "normalized": [] }, { "id": "4115", "type": "protein_molecule", "text": [ "TAL1" ], "offsets": [ [ 1373, 1377 ] ], "normalized": [] }, { "id": "4116", "type": "DNA_family_or_group", "text": [ "TAL1 alleles" ], "offsets": [ [ 1422, 1434 ] ], "normalized": [] }, { "id": "4117", "type": "protein_molecule", "text": [ "TAL1" ], "offsets": [ [ 1422, 1426 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "4119", "type": "title", "text": [ "Expression of erythroid-specific genes in acute megakaryoblastic leukaemia and transient myeloproliferative disorder in Down's syndrome." ], "offsets": [ [ 0, 136 ] ] }, { "id": "4120", "type": "abstract", "text": [ "Acute megakaryoblastic leukaemia (M7) and transient myeloproliferative disorder in Down's syndrome (TMD) are characterized by rapid growth of abnormal blast cells which express megakaryocytic markers. To clarify properties of the blast cells in M7 and TMD cases, we examined erythroid markers expression in blasts from six cases with M7 and seven cases with TMD in this study. Erythroid-specific mRNAs encoding gamma-globin and erythroid delta-aminolevulinate synthase were found to be expressed in blasts from most of these cases, indicating that majorities of the blasts in M7 and TMD cases have erythroid and megakaryocytic phenotypes. We also found that mRNAs encoding GATA-1 and GATA-2 are expressed in all these cases. These results suggest that M7 blasts and TMD blasts correspond to the erythroid/megakaryocytic bipotential progenitor cells." ], "offsets": [ [ 137, 986 ] ] } ]

[ { "id": "4121", "type": "DNA_family_or_group", "text": [ "erythroid-specific genes" ], "offsets": [ [ 14, 38 ] ], "normalized": [] }, { "id": "4122", "type": "other_name", "text": [ "acute megakaryoblastic leukaemia" ], "offsets": [ [ 42, 74 ] ], "normalized": [] }, { "id": "4123", "type": "other_name", "text": [ "transient myeloproliferative disorder" ], "offsets": [ [ 79, 116 ] ], "normalized": [] }, { "id": "4124", "type": "other_name", "text": [ "Down's syndrome" ], "offsets": [ [ 120, 135 ] ], "normalized": [] }, { "id": "4125", "type": "other_name", "text": [ "Acute megakaryoblastic leukaemia" ], "offsets": [ [ 137, 169 ] ], "normalized": [] }, { "id": "4126", "type": "other_name", "text": [ "M7" ], "offsets": [ [ 171, 173 ] ], "normalized": [] }, { "id": "4127", "type": "other_name", "text": [ "transient myeloproliferative disorder" ], "offsets": [ [ 179, 216 ] ], "normalized": [] }, { "id": "4128", "type": "other_name", "text": [ "Down's syndrome" ], "offsets": [ [ 220, 235 ] ], "normalized": [] }, { "id": "4129", "type": "other_name", "text": [ "TMD" ], "offsets": [ [ 237, 240 ] ], "normalized": [] }, { "id": "4130", "type": "cell_type", "text": [ "abnormal blast cells" ], "offsets": [ [ 279, 299 ] ], "normalized": [] }, { "id": "4131", "type": "protein_family_or_group", "text": [ "megakaryocytic markers" ], "offsets": [ [ 314, 336 ] ], "normalized": [] }, { "id": "4132", "type": "cell_type", "text": [ "blast cells" ], "offsets": [ [ 367, 378 ] ], "normalized": [] }, { "id": "4133", "type": "other_name", "text": [ "M7" ], "offsets": [ [ 382, 384 ] ], "normalized": [] }, { "id": "4134", "type": "other_name", "text": [ "TMD" ], "offsets": [ [ 389, 392 ] ], "normalized": [] }, { "id": "4135", "type": "other_name", "text": [ "erythroid markers expression" ], "offsets": [ [ 412, 440 ] ], "normalized": [] }, { "id": "4136", "type": "cell_type", "text": [ "blasts" ], "offsets": [ [ 444, 450 ] ], "normalized": [] }, { "id": "4137", "type": "other_name", "text": [ "M7" ], "offsets": [ [ 471, 473 ] ], "normalized": [] }, { "id": "4138", "type": "other_name", "text": [ "TMD" ], "offsets": [ [ 495, 498 ] ], "normalized": [] }, { "id": "4139", "type": "RNA_family_or_group", "text": [ "Erythroid-specific mRNAs" ], "offsets": [ [ 514, 538 ] ], "normalized": [] }, { "id": "4140", "type": "protein_family_or_group", "text": [ "gamma-globin" ], "offsets": [ [ 548, 560 ] ], "normalized": [] }, { "id": "4141", "type": "protein_molecule", "text": [ "erythroid delta-aminolevulinate synthase" ], "offsets": [ [ 565, 605 ] ], "normalized": [] }, { "id": "4142", "type": "cell_type", "text": [ "blasts" ], "offsets": [ [ 636, 642 ] ], "normalized": [] }, { "id": "4143", "type": "cell_type", "text": [ "blasts" ], "offsets": [ [ 703, 709 ] ], "normalized": [] }, { "id": "4144", "type": "other_name", "text": [ "M7" ], "offsets": [ [ 713, 715 ] ], "normalized": [] }, { "id": "4145", "type": "other_name", "text": [ "TMD" ], "offsets": [ [ 720, 723 ] ], "normalized": [] }, { "id": "4146", "type": "(AND other_name other_name)", "text": [ "erythroid and megakaryocytic phenotypes" ], "offsets": [ [ 735, 774 ] ], "normalized": [] }, { "id": "4147", "type": "", "text": [ "erythroid" ], "offsets": [ [ 565, 574 ] ], "normalized": [] }, { "id": "4148", "type": "", "text": [ "megakaryocytic" ], "offsets": [ [ 749, 763 ] ], "normalized": [] }, { "id": "4149", "type": "", "text": [ "phenotypes" ], "offsets": [ [ 764, 774 ] ], "normalized": [] }, { "id": "4150", "type": "RNA_family_or_group", "text": [ "mRNAs" ], "offsets": [ [ 795, 800 ] ], "normalized": [] }, { "id": "4151", "type": "protein_molecule", "text": [ "GATA-1" ], "offsets": [ [ 810, 816 ] ], "normalized": [] }, { "id": "4152", "type": "protein_molecule", "text": [ "GATA-2" ], "offsets": [ [ 821, 827 ] ], "normalized": [] }, { "id": "4153", "type": "cell_type", "text": [ "M7 blasts" ], "offsets": [ [ 889, 898 ] ], "normalized": [] }, { "id": "4154", "type": "other_name", "text": [ "M7" ], "offsets": [ [ 889, 891 ] ], "normalized": [] }, { "id": "4155", "type": "cell_type", "text": [ "TMD blasts" ], "offsets": [ [ 903, 913 ] ], "normalized": [] }, { "id": "4156", "type": "other_name", "text": [ "TMD" ], "offsets": [ [ 903, 906 ] ], "normalized": [] }, { "id": "4157", "type": "cell_type", "text": [ "erythroid/megakaryocytic bipotential progenitor cells" ], "offsets": [ [ 932, 985 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "4159", "type": "title", "text": [ "Expression of Ah receptor (TCDD receptor) during human monocytic differentiation." ], "offsets": [ [ 0, 81 ] ] }, { "id": "4160", "type": "abstract", "text": [ "We have previously found a high expression of human Ah receptor (TCDD receptor) mRNA in peripheral blood cells of individuals. In this paper, the expression of this gene in blood cells was first investigated in fractions of nucleated cells, revealing predominant expression of the Ah receptor gene in the monocyte fraction. Then the expression levels of AhR mRNA in various hematopoietic cell lines were examined together with those of Arnt and P450IA1. AhR was expressed at high levels in monocytoid U937, THP1, and HEL/S cells, and at moderate levels in promyelocytic HL60 cells and erythroblastic HEL cells. However, it was not detected in lymphoid cells MOLT4 (T cell) and BALL1 (B cell), nor in K562 erythroblasts. Furthermore, a specific induction of AhR during monocytic differentiation was investigated in HL60 and HEL cells. HL60 cells were induced to differentiate toward monocytes-macrophages by incubation with phorbol ester, showing a 5- to 2-fold increase of AhR mRNA. The incubation with transforming growth factor beta 1 and 1 alpha,25-dihydroxyvitamin D3 resulted in a 5- to 7-fold increase of AhR mRNA. The HEL cells also exhibited a similar elevation of AhR mRNA level, when they had differentiated toward monocyte-macrophage cells by these combined inducers, but little change in the mRNA level was observed when the cells were induced to differentiate into other cell types. Treatment of the differentiated HL60 cells with 3-methylcholanthrene, a ligand of AhR, induced the expression of the P450IA1 gene. These results indicated that expression of AhR mRNA was significantly induced during monocytic differentiation and that the differentiated cells were responsive to xenobiotics. Our results suggest that AhR may play an important role in the function of monocytes and also in the eventual activation of environmental carcinogens." ], "offsets": [ [ 82, 1936 ] ] } ]

[ { "id": "4161", "type": "protein_molecule", "text": [ "Ah receptor" ], "offsets": [ [ 14, 25 ] ], "normalized": [] }, { "id": "4162", "type": "protein_molecule", "text": [ "TCDD receptor" ], "offsets": [ [ 27, 40 ] ], "normalized": [] }, { "id": "4163", "type": "other_name", "text": [ "human monocytic differentiation" ], "offsets": [ [ 49, 80 ] ], "normalized": [] }, { "id": "4164", "type": "RNA_molecule", "text": [ "human Ah receptor (TCDD receptor) mRNA" ], "offsets": [ [ 128, 166 ] ], "normalized": [] }, { "id": "4165", "type": "protein_molecule", "text": [ "human Ah receptor" ], "offsets": [ [ 128, 145 ] ], "normalized": [] }, { "id": "4166", "type": "protein_molecule", "text": [ "Ah receptor" ], "offsets": [ [ 134, 145 ] ], "normalized": [] }, { "id": "4167", "type": "protein_molecule", "text": [ "TCDD receptor" ], "offsets": [ [ 147, 160 ] ], "normalized": [] }, { "id": "4168", "type": "cell_type", "text": [ "peripheral blood cells" ], "offsets": [ [ 170, 192 ] ], "normalized": [] }, { "id": "4169", "type": "multi_cell", "text": [ "individuals" ], "offsets": [ [ 196, 207 ] ], "normalized": [] }, { "id": "4170", "type": "cell_type", "text": [ "blood cells" ], "offsets": [ [ 255, 266 ] ], "normalized": [] }, { "id": "4171", "type": "cell_type", "text": [ "nucleated cells" ], "offsets": [ [ 306, 321 ] ], "normalized": [] }, { "id": "4172", "type": "DNA_domain_or_region", "text": [ "Ah receptor gene" ], "offsets": [ [ 363, 379 ] ], "normalized": [] }, { "id": "4173", "type": "protein_molecule", "text": [ "Ah receptor" ], "offsets": [ [ 363, 374 ] ], "normalized": [] }, { "id": "4174", "type": "cell_type", "text": [ "monocyte fraction" ], "offsets": [ [ 387, 404 ] ], "normalized": [] }, { "id": "4175", "type": "other_name", "text": [ "expression levels" ], "offsets": [ [ 415, 432 ] ], "normalized": [] }, { "id": "4176", "type": "RNA_molecule", "text": [ "AhR mRNA" ], "offsets": [ [ 436, 444 ] ], "normalized": [] }, { "id": "4177", "type": "cell_line", "text": [ "hematopoietic cell lines" ], "offsets": [ [ 456, 480 ] ], "normalized": [] }, { "id": "4178", "type": "protein_molecule", "text": [ "Arnt" ], "offsets": [ [ 518, 522 ] ], "normalized": [] }, { "id": "4179", "type": "protein_molecule", "text": [ "P450IA1" ], "offsets": [ [ 527, 534 ] ], "normalized": [] }, { "id": "4180", "type": "protein_molecule", "text": [ "AhR" ], "offsets": [ [ 536, 539 ] ], "normalized": [] }, { "id": "4181", "type": "cell_line", "text": [ "monocytoid U937" ], "offsets": [ [ 572, 587 ] ], "normalized": [] }, { "id": "4182", "type": "cell_line", "text": [ "THP1" ], "offsets": [ [ 589, 593 ] ], "normalized": [] }, { "id": "4183", "type": "cell_line", "text": [ "HEL/S cells" ], "offsets": [ [ 599, 610 ] ], "normalized": [] }, { "id": "4184", "type": "cell_line", "text": [ "promyelocytic HL60 cells" ], "offsets": [ [ 638, 662 ] ], "normalized": [] }, { "id": "4185", "type": "cell_line", "text": [ "erythroblastic HEL cells" ], "offsets": [ [ 667, 691 ] ], "normalized": [] }, { "id": "4186", "type": "cell_type", "text": [ "lymphoid cells" ], "offsets": [ [ 725, 739 ] ], "normalized": [] }, { "id": "4187", "type": "cell_line", "text": [ "MOLT4" ], "offsets": [ [ 740, 745 ] ], "normalized": [] }, { "id": "4188", "type": "cell_type", "text": [ "T cell" ], "offsets": [ [ 747, 753 ] ], "normalized": [] }, { "id": "4189", "type": "cell_line", "text": [ "BALL1" ], "offsets": [ [ 759, 764 ] ], "normalized": [] }, { "id": "4190", "type": "cell_type", "text": [ "B cell" ], "offsets": [ [ 766, 772 ] ], "normalized": [] }, { "id": "4191", "type": "cell_line", "text": [ "K562 erythroblasts" ], "offsets": [ [ 782, 800 ] ], "normalized": [] }, { "id": "4192", "type": "protein_molecule", "text": [ "AhR" ], "offsets": [ [ 839, 842 ] ], "normalized": [] }, { "id": "4193", "type": "cell_line", "text": [ "HL60" ], "offsets": [ [ 896, 900 ] ], "normalized": [] }, { "id": "4194", "type": "cell_line", "text": [ "HEL cells" ], "offsets": [ [ 905, 914 ] ], "normalized": [] }, { "id": "4195", "type": "cell_line", "text": [ "HL60 cells" ], "offsets": [ [ 916, 926 ] ], "normalized": [] }, { "id": "4196", "type": "cell_type", "text": [ "monocytes-macrophages" ], "offsets": [ [ 964, 985 ] ], "normalized": [] }, { "id": "4197", "type": "RNA_molecule", "text": [ "AhR mRNA" ], "offsets": [ [ 1055, 1063 ] ], "normalized": [] }, { "id": "4198", "type": "protein_molecule", "text": [ "AhR" ], "offsets": [ [ 1055, 1058 ] ], "normalized": [] }, { "id": "4199", "type": "protein_molecule", "text": [ "transforming growth factor beta 1" ], "offsets": [ [ 1085, 1118 ] ], "normalized": [] }, { "id": "4200", "type": "lipid", "text": [ "1 alpha,25-dihydroxyvitamin D3" ], "offsets": [ [ 1123, 1153 ] ], "normalized": [] }, { "id": "4201", "type": "RNA_molecule", "text": [ "AhR mRNA" ], "offsets": [ [ 1193, 1201 ] ], "normalized": [] }, { "id": "4202", "type": "protein_molecule", "text": [ "AhR" ], "offsets": [ [ 1193, 1196 ] ], "normalized": [] }, { "id": "4203", "type": "cell_line", "text": [ "HEL cells" ], "offsets": [ [ 1207, 1216 ] ], "normalized": [] }, { "id": "4204", "type": "other_name", "text": [ "AhR mRNA level" ], "offsets": [ [ 1255, 1269 ] ], "normalized": [] }, { "id": "4205", "type": "RNA_molecule", "text": [ "AhR mRNA" ], "offsets": [ [ 1255, 1263 ] ], "normalized": [] }, { "id": "4206", "type": "protein_molecule", "text": [ "AhR" ], "offsets": [ [ 1255, 1258 ] ], "normalized": [] }, { "id": "4207", "type": "cell_type", "text": [ "monocyte-macrophage cells" ], "offsets": [ [ 1307, 1332 ] ], "normalized": [] }, { "id": "4208", "type": "other_name", "text": [ "mRNA level" ], "offsets": [ [ 1259, 1269 ] ], "normalized": [] }, { "id": "4209", "type": "cell_line", "text": [ "differentiated HL60 cells" ], "offsets": [ [ 1495, 1520 ] ], "normalized": [] }, { "id": "4210", "type": "cell_line", "text": [ "HL60" ], "offsets": [ [ 1510, 1514 ] ], "normalized": [] }, { "id": "4211", "type": "other_organic_compound", "text": [ "3-methylcholanthrene" ], "offsets": [ [ 1526, 1546 ] ], "normalized": [] }, { "id": "4212", "type": "protein_molecule", "text": [ "AhR" ], "offsets": [ [ 1560, 1563 ] ], "normalized": [] }, { "id": "4213", "type": "protein_molecule", "text": [ "P450IA1" ], "offsets": [ [ 1595, 1602 ] ], "normalized": [] }, { "id": "4214", "type": "RNA_molecule", "text": [ "AhR mRNA" ], "offsets": [ [ 1652, 1660 ] ], "normalized": [] }, { "id": "4215", "type": "protein_molecule", "text": [ "AhR" ], "offsets": [ [ 1652, 1655 ] ], "normalized": [] }, { "id": "4216", "type": "other_name", "text": [ "monocytic differentiation" ], "offsets": [ [ 1694, 1719 ] ], "normalized": [] }, { "id": "4217", "type": "cell_type", "text": [ "differentiated cells" ], "offsets": [ [ 1733, 1753 ] ], "normalized": [] }, { "id": "4218", "type": "other_organic_compound", "text": [ "xenobiotics" ], "offsets": [ [ 1773, 1784 ] ], "normalized": [] }, { "id": "4219", "type": "protein_molecule", "text": [ "AhR" ], "offsets": [ [ 1811, 1814 ] ], "normalized": [] }, { "id": "4220", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 1861, 1870 ] ], "normalized": [] }, { "id": "4221", "type": "other_organic_compound", "text": [ "environmental carcinogens" ], "offsets": [ [ 1910, 1935 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "4223", "type": "title", "text": [ "Neutrophils and monocytes express high levels of PU.1 (Spi-1) but not Spi-B." ], "offsets": [ [ 0, 76 ] ] }, { "id": "4224", "type": "abstract", "text": [ "PU.1 (the Spi-1 oncogene) and Spi-B are closely related members of the ets transcription factor family, sharing similar DNA binding specificities mediated by similar DNA binding domains. PU.1 and Spi-B have been previously described as being predominantly expressed coordinately in macrophages and B cells, but their expression in early hematopoietic stages and during the course of myeloid differentiation to monocytes and macrophages or to neutrophils has not been extensively investigated. Here, we report that PU.1 mRNA is upregulated during myeloid differentiation of human purified CD34+ cells and murine multipotential FDCP-mix A4 cells, suggesting that PU.1 is upregulated as an early event during differentiation of multipotential progenitor cells. PU.1 expression is maintained at stable levels during differentiation of myeloid cell lines U937 and HL-60 to monocytic and neutrophilic cells. PU.1 is expressed at highest levels in mature human monocytes and human peripheral blood neutrophils. In contrast to PU.1, significant levels of Spi-B mRNA and protein are found only in some B-cell lines and spleen but are not found in myeloid cell lines, neutrophils, or macrophages. In vitro translated Spi-B protein can bind to PU.1 binding sites in myeloid promoters and transactivate these promoters in nonmyeloid cells. Therefore, although PU.1 and Spi-B may bind to similar DNA control elements and have redundancy of transactivation function in vitro, the lack of significant levels of Spi-B in myeloid cells makes it unlikely that Spi-B plays a significant role in myeloid lineage development and gene expression. In contrast, PU.1 is expressed at high levels not only in monocytes and macrophages but also in neutrophils, indicating that PU.1 can activate gene expression in both major myeloid lineages." ], "offsets": [ [ 77, 1892 ] ] } ]

[ { "id": "4225", "type": "cell_type", "text": [ "Neutrophils" ], "offsets": [ [ 0, 11 ] ], "normalized": [] }, { "id": "4226", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 16, 25 ] ], "normalized": [] }, { "id": "4227", "type": "protein_molecule", "text": [ "PU.1" ], "offsets": [ [ 49, 53 ] ], "normalized": [] }, { "id": "4228", "type": "protein_molecule", "text": [ "Spi-1" ], "offsets": [ [ 55, 60 ] ], "normalized": [] }, { "id": "4229", "type": "protein_molecule", "text": [ "Spi-B" ], "offsets": [ [ 70, 75 ] ], "normalized": [] }, { "id": "4230", "type": "protein_molecule", "text": [ "PU.1" ], "offsets": [ [ 77, 81 ] ], "normalized": [] }, { "id": "4231", "type": "DNA_domain_or_region", "text": [ "Spi-1 oncogene" ], "offsets": [ [ 87, 101 ] ], "normalized": [] }, { "id": "4232", "type": "protein_molecule", "text": [ "Spi-B" ], "offsets": [ [ 107, 112 ] ], "normalized": [] }, { "id": "4233", "type": "protein_family_or_group", "text": [ "ets transcription factor family" ], "offsets": [ [ 148, 179 ] ], "normalized": [] }, { "id": "4234", "type": "other_name", "text": [ "DNA binding specificities" ], "offsets": [ [ 197, 222 ] ], "normalized": [] }, { "id": "4235", "type": "protein_domain_or_region", "text": [ "DNA binding domains" ], "offsets": [ [ 243, 262 ] ], "normalized": [] }, { "id": "4236", "type": "protein_molecule", "text": [ "PU.1" ], "offsets": [ [ 264, 268 ] ], "normalized": [] }, { "id": "4237", "type": "protein_molecule", "text": [ "Spi-B" ], "offsets": [ [ 273, 278 ] ], "normalized": [] }, { "id": "4238", "type": "cell_type", "text": [ "macrophages" ], "offsets": [ [ 359, 370 ] ], "normalized": [] }, { "id": "4239", "type": "cell_type", "text": [ "B cells" ], "offsets": [ [ 375, 382 ] ], "normalized": [] }, { "id": "4240", "type": "other_name", "text": [ "early hematopoietic stages" ], "offsets": [ [ 408, 434 ] ], "normalized": [] }, { "id": "4241", "type": "other_name", "text": [ "myeloid differentiation" ], "offsets": [ [ 460, 483 ] ], "normalized": [] }, { "id": "4242", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 487, 496 ] ], "normalized": [] }, { "id": "4243", "type": "cell_type", "text": [ "macrophages" ], "offsets": [ [ 501, 512 ] ], "normalized": [] }, { "id": "4244", "type": "cell_type", "text": [ "neutrophils" ], "offsets": [ [ 519, 530 ] ], "normalized": [] }, { "id": "4245", "type": "RNA_molecule", "text": [ "PU.1 mRNA" ], "offsets": [ [ 591, 600 ] ], "normalized": [] }, { "id": "4246", "type": "protein_molecule", "text": [ "PU.1" ], "offsets": [ [ 591, 595 ] ], "normalized": [] }, { "id": "4247", "type": "other_name", "text": [ "myeloid differentiation" ], "offsets": [ [ 623, 646 ] ], "normalized": [] }, { "id": "4248", "type": "cell_line", "text": [ "human purified CD34+ cells" ], "offsets": [ [ 650, 676 ] ], "normalized": [] }, { "id": "4249", "type": "cell_line", "text": [ "murine multipotential FDCP-mix A4 cells" ], "offsets": [ [ 681, 720 ] ], "normalized": [] }, { "id": "4250", "type": "protein_molecule", "text": [ "PU.1" ], "offsets": [ [ 738, 742 ] ], "normalized": [] }, { "id": "4251", "type": "other_name", "text": [ "differentiation" ], "offsets": [ [ 631, 646 ] ], "normalized": [] }, { "id": "4252", "type": "cell_type", "text": [ "multipotential progenitor cells" ], "offsets": [ [ 802, 833 ] ], "normalized": [] }, { "id": "4253", "type": "protein_molecule", "text": [ "PU.1" ], "offsets": [ [ 835, 839 ] ], "normalized": [] }, { "id": "4254", "type": "cell_line", "text": [ "myeloid cell lines" ], "offsets": [ [ 908, 926 ] ], "normalized": [] }, { "id": "4255", "type": "cell_line", "text": [ "U937" ], "offsets": [ [ 927, 931 ] ], "normalized": [] }, { "id": "4256", "type": "cell_line", "text": [ "HL-60" ], "offsets": [ [ 936, 941 ] ], "normalized": [] }, { "id": "4257", "type": "(AND cell_type cell_type)", "text": [ "monocytic and neutrophilic cells" ], "offsets": [ [ 945, 977 ] ], "normalized": [] }, { "id": "4258", "type": "", "text": [ "monocytic" ], "offsets": [ [ 945, 954 ] ], "normalized": [] }, { "id": "4259", "type": "", "text": [ "neutrophilic" ], "offsets": [ [ 959, 971 ] ], "normalized": [] }, { "id": "4260", "type": "", "text": [ "cells" ], "offsets": [ [ 972, 977 ] ], "normalized": [] }, { "id": "4261", "type": "protein_molecule", "text": [ "PU.1" ], "offsets": [ [ 979, 983 ] ], "normalized": [] }, { "id": "4262", "type": "cell_type", "text": [ "mature human monocytes" ], "offsets": [ [ 1018, 1040 ] ], "normalized": [] }, { "id": "4263", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 1031, 1040 ] ], "normalized": [] }, { "id": "4264", "type": "cell_type", "text": [ "human peripheral blood neutrophils" ], "offsets": [ [ 1045, 1079 ] ], "normalized": [] }, { "id": "4265", "type": "cell_type", "text": [ "neutrophils" ], "offsets": [ [ 1068, 1079 ] ], "normalized": [] }, { "id": "4266", "type": "protein_molecule", "text": [ "PU.1" ], "offsets": [ [ 1096, 1100 ] ], "normalized": [] }, { "id": "4267", "type": "RNA_molecule", "text": [ "Spi-B mRNA" ], "offsets": [ [ 1124, 1134 ] ], "normalized": [] }, { "id": "4268", "type": "protein_molecule", "text": [ "Spi-B" ], "offsets": [ [ 1124, 1129 ] ], "normalized": [] }, { "id": "4269", "type": "cell_line", "text": [ "B-cell lines" ], "offsets": [ [ 1170, 1182 ] ], "normalized": [] }, { "id": "4270", "type": "body_part", "text": [ "spleen" ], "offsets": [ [ 1187, 1193 ] ], "normalized": [] }, { "id": "4271", "type": "cell_line", "text": [ "myeloid cell lines" ], "offsets": [ [ 1215, 1233 ] ], "normalized": [] }, { "id": "4272", "type": "cell_type", "text": [ "neutrophils" ], "offsets": [ [ 1235, 1246 ] ], "normalized": [] }, { "id": "4273", "type": "cell_type", "text": [ "macrophages" ], "offsets": [ [ 1251, 1262 ] ], "normalized": [] }, { "id": "4274", "type": "protein_molecule", "text": [ "Spi-B protein" ], "offsets": [ [ 1284, 1297 ] ], "normalized": [] }, { "id": "4275", "type": "protein_molecule", "text": [ "Spi-B" ], "offsets": [ [ 1284, 1289 ] ], "normalized": [] }, { "id": "4276", "type": "DNA_domain_or_region", "text": [ "PU.1 binding sites" ], "offsets": [ [ 1310, 1328 ] ], "normalized": [] }, { "id": "4277", "type": "protein_molecule", "text": [ "PU.1" ], "offsets": [ [ 1310, 1314 ] ], "normalized": [] }, { "id": "4278", "type": "DNA_domain_or_region", "text": [ "myeloid promoters" ], "offsets": [ [ 1332, 1349 ] ], "normalized": [] }, { "id": "4279", "type": "DNA_family_or_group", "text": [ "promoters" ], "offsets": [ [ 1340, 1349 ] ], "normalized": [] }, { "id": "4280", "type": "cell_type", "text": [ "nonmyeloid cells" ], "offsets": [ [ 1387, 1403 ] ], "normalized": [] }, { "id": "4281", "type": "protein_molecule", "text": [ "PU.1" ], "offsets": [ [ 1425, 1429 ] ], "normalized": [] }, { "id": "4282", "type": "protein_molecule", "text": [ "Spi-B" ], "offsets": [ [ 1434, 1439 ] ], "normalized": [] }, { "id": "4283", "type": "other_name", "text": [ "transactivation function" ], "offsets": [ [ 1504, 1528 ] ], "normalized": [] }, { "id": "4284", "type": "protein_molecule", "text": [ "Spi-B" ], "offsets": [ [ 1573, 1578 ] ], "normalized": [] }, { "id": "4285", "type": "cell_type", "text": [ "myeloid cells" ], "offsets": [ [ 1582, 1595 ] ], "normalized": [] }, { "id": "4286", "type": "protein_molecule", "text": [ "Spi-B" ], "offsets": [ [ 1619, 1624 ] ], "normalized": [] }, { "id": "4287", "type": "other_name", "text": [ "myeloid lineage development" ], "offsets": [ [ 1653, 1680 ] ], "normalized": [] }, { "id": "4288", "type": "other_name", "text": [ "gene expression" ], "offsets": [ [ 1685, 1700 ] ], "normalized": [] }, { "id": "4289", "type": "protein_molecule", "text": [ "PU.1" ], "offsets": [ [ 1715, 1719 ] ], "normalized": [] }, { "id": "4290", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 1760, 1769 ] ], "normalized": [] }, { "id": "4291", "type": "cell_type", "text": [ "macrophages" ], "offsets": [ [ 1774, 1785 ] ], "normalized": [] }, { "id": "4292", "type": "cell_type", "text": [ "neutrophils" ], "offsets": [ [ 1798, 1809 ] ], "normalized": [] }, { "id": "4293", "type": "protein_molecule", "text": [ "PU.1" ], "offsets": [ [ 1827, 1831 ] ], "normalized": [] }, { "id": "4294", "type": "other_name", "text": [ "gene expression" ], "offsets": [ [ 1845, 1860 ] ], "normalized": [] }, { "id": "4295", "type": "cell_type", "text": [ "major myeloid lineages" ], "offsets": [ [ 1869, 1891 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "4297", "type": "title", "text": [ "Identification of a major positive regulatory element located 5' to the human zeta-globin gene." ], "offsets": [ [ 0, 95 ] ] }, { "id": "4298", "type": "abstract", "text": [ "The function of the zeta-globin promoter was studied using a series of zeta-globin promoter deletion constructs to drive luciferase expression in transiently transfected human erythroleukemia cells. The promoters were used without enhancers, or with enhancers derived from the beta-globin locus control region and the alpha-globin HS-40 enhancer. When transfected into K562 cells, which express zeta-globin, comparable amounts of activity were obtained from the -557 and -417 zeta-luciferase constructs and the alpha-luciferase constructs when no enhancers or the alpha-globin locus enhancers were used. When the constructs were transfected into OCIM1 cells, which do not express zeta-globin, the zeta-globin promoters were at best 20% as active as the alpha-globin promoters. When sequences from -417 to -207 5' to the zeta-globin mRNA cap site were deleted, up to 95% of the zeta-globin promoter activity was lost in K562 cells. Reinsertion of these sequences into zeta-luciferase constructs missing the -417 to -207 region showed that the sequences lack classical enhancer activity. Point mutation of a GATA-1 site at -230 reduced promoter activity by 37%. Point mutation of a CCACC site at -240 had no effect. Electrophoretic mobility shift assays indicated that the -230 GATA-1 site has a relatively low affinity for GATA-1. These experiments show the presence of a strong positive-acting element, located between -417 and -207 bp 5' to the zeta-globin mRNA cap site, is necessary for high-level promoter activity in K562 cells. This element requires GATA-1 and additional unknown factors for maximal activity." ], "offsets": [ [ 96, 1711 ] ] } ]

[ { "id": "4299", "type": "DNA_family_or_group", "text": [ "positive regulatory element" ], "offsets": [ [ 26, 53 ] ], "normalized": [] }, { "id": "4300", "type": "DNA_domain_or_region", "text": [ "human zeta-globin gene" ], "offsets": [ [ 72, 94 ] ], "normalized": [] }, { "id": "4301", "type": "DNA_domain_or_region", "text": [ "zeta-globin promoter" ], "offsets": [ [ 116, 136 ] ], "normalized": [] }, { "id": "4302", "type": "DNA_molecule", "text": [ "zeta-globin promoter deletion constructs" ], "offsets": [ [ 167, 207 ] ], "normalized": [] }, { "id": "4303", "type": "DNA_domain_or_region", "text": [ "zeta-globin promoter" ], "offsets": [ [ 167, 187 ] ], "normalized": [] }, { "id": "4304", "type": "other_name", "text": [ "luciferase expression" ], "offsets": [ [ 217, 238 ] ], "normalized": [] }, { "id": "4305", "type": "protein_molecule", "text": [ "luciferase" ], "offsets": [ [ 217, 227 ] ], "normalized": [] }, { "id": "4306", "type": "cell_line", "text": [ "transiently transfected human erythroleukemia cells" ], "offsets": [ [ 242, 293 ] ], "normalized": [] }, { "id": "4307", "type": "DNA_family_or_group", "text": [ "promoters" ], "offsets": [ [ 299, 308 ] ], "normalized": [] }, { "id": "4308", "type": "DNA_family_or_group", "text": [ "enhancers" ], "offsets": [ [ 327, 336 ] ], "normalized": [] }, { "id": "4309", "type": "DNA_family_or_group", "text": [ "enhancers" ], "offsets": [ [ 346, 355 ] ], "normalized": [] }, { "id": "4310", "type": "DNA_domain_or_region", "text": [ "beta-globin locus control region" ], "offsets": [ [ 373, 405 ] ], "normalized": [] }, { "id": "4311", "type": "DNA_domain_or_region", "text": [ "alpha-globin HS-40 enhancer" ], "offsets": [ [ 414, 441 ] ], "normalized": [] }, { "id": "4312", "type": "cell_line", "text": [ "K562 cells" ], "offsets": [ [ 465, 475 ] ], "normalized": [] }, { "id": "4313", "type": "protein_family_or_group", "text": [ "zeta-globin" ], "offsets": [ [ 491, 502 ] ], "normalized": [] }, { "id": "4314", "type": "DNA_molecule", "text": [ "-557 and -417 zeta-luciferase constructs" ], "offsets": [ [ 558, 598 ] ], "normalized": [] }, { "id": "4315", "type": "protein_molecule", "text": [ "luciferase" ], "offsets": [ [ 577, 587 ] ], "normalized": [] }, { "id": "4316", "type": "DNA_molecule", "text": [ "alpha-luciferase constructs" ], "offsets": [ [ 607, 634 ] ], "normalized": [] }, { "id": "4317", "type": "protein_molecule", "text": [ "luciferase" ], "offsets": [ [ 613, 623 ] ], "normalized": [] }, { "id": "4318", "type": "DNA_family_or_group", "text": [ "enhancers" ], "offsets": [ [ 643, 652 ] ], "normalized": [] }, { "id": "4319", "type": "DNA_domain_or_region", "text": [ "alpha-globin locus enhancers" ], "offsets": [ [ 660, 688 ] ], "normalized": [] }, { "id": "4320", "type": "DNA_family_or_group", "text": [ "enhancers" ], "offsets": [ [ 679, 688 ] ], "normalized": [] }, { "id": "4321", "type": "cell_line", "text": [ "OCIM1 cells" ], "offsets": [ [ 742, 753 ] ], "normalized": [] }, { "id": "4322", "type": "protein_family_or_group", "text": [ "zeta-globin" ], "offsets": [ [ 776, 787 ] ], "normalized": [] }, { "id": "4323", "type": "DNA_domain_or_region", "text": [ "zeta-globin promoters" ], "offsets": [ [ 793, 814 ] ], "normalized": [] }, { "id": "4324", "type": "protein_family_or_group", "text": [ "zeta-globin" ], "offsets": [ [ 793, 804 ] ], "normalized": [] }, { "id": "4325", "type": "DNA_family_or_group", "text": [ "alpha-globin promoters" ], "offsets": [ [ 849, 871 ] ], "normalized": [] }, { "id": "4326", "type": "DNA_family_or_group", "text": [ "promoters" ], "offsets": [ [ 805, 814 ] ], "normalized": [] }, { "id": "4327", "type": "DNA_domain_or_region", "text": [ "sequences from -417 to -207 5'" ], "offsets": [ [ 878, 908 ] ], "normalized": [] }, { "id": "4328", "type": "RNA_domain_or_region", "text": [ "zeta-globin mRNA cap site" ], "offsets": [ [ 916, 941 ] ], "normalized": [] }, { "id": "4329", "type": "RNA_molecule", "text": [ "zeta-globin mRNA" ], "offsets": [ [ 916, 932 ] ], "normalized": [] }, { "id": "4330", "type": "DNA_domain_or_region", "text": [ "zeta-globin promoter" ], "offsets": [ [ 973, 993 ] ], "normalized": [] }, { "id": "4331", "type": "protein_family_or_group", "text": [ "zeta-globin" ], "offsets": [ [ 916, 927 ] ], "normalized": [] }, { "id": "4332", "type": "cell_line", "text": [ "K562 cells" ], "offsets": [ [ 1015, 1025 ] ], "normalized": [] }, { "id": "4333", "type": "DNA_family_or_group", "text": [ "zeta-luciferase constructs" ], "offsets": [ [ 1063, 1089 ] ], "normalized": [] }, { "id": "4334", "type": "protein_molecule", "text": [ "luciferase" ], "offsets": [ [ 1068, 1078 ] ], "normalized": [] }, { "id": "4335", "type": "other_name", "text": [ "classical enhancer activity" ], "offsets": [ [ 1153, 1180 ] ], "normalized": [] }, { "id": "4336", "type": "other_name", "text": [ "Point mutation" ], "offsets": [ [ 1182, 1196 ] ], "normalized": [] }, { "id": "4337", "type": "DNA_domain_or_region", "text": [ "GATA-1 site" ], "offsets": [ [ 1202, 1213 ] ], "normalized": [] }, { "id": "4338", "type": "protein_molecule", "text": [ "GATA-1" ], "offsets": [ [ 1202, 1208 ] ], "normalized": [] }, { "id": "4339", "type": "other_name", "text": [ "promoter activity" ], "offsets": [ [ 1230, 1247 ] ], "normalized": [] }, { "id": "4340", "type": "other_name", "text": [ "Point mutation" ], "offsets": [ [ 1256, 1270 ] ], "normalized": [] }, { "id": "4341", "type": "DNA_domain_or_region", "text": [ "CCACC site" ], "offsets": [ [ 1276, 1286 ] ], "normalized": [] }, { "id": "4342", "type": "other_name", "text": [ "Electrophoretic mobility shift assays" ], "offsets": [ [ 1310, 1347 ] ], "normalized": [] }, { "id": "4343", "type": "DNA_domain_or_region", "text": [ "-230 GATA-1 site" ], "offsets": [ [ 1367, 1383 ] ], "normalized": [] }, { "id": "4344", "type": "protein_molecule", "text": [ "GATA-1" ], "offsets": [ [ 1372, 1378 ] ], "normalized": [] }, { "id": "4345", "type": "protein_molecule", "text": [ "GATA-1" ], "offsets": [ [ 1418, 1424 ] ], "normalized": [] }, { "id": "4346", "type": "DNA_domain_or_region", "text": [ "positive-acting element" ], "offsets": [ [ 1474, 1497 ] ], "normalized": [] }, { "id": "4347", "type": "DNA_domain_or_region", "text": [ "-417 and -207 bp 5'" ], "offsets": [ [ 1515, 1534 ] ], "normalized": [] }, { "id": "4348", "type": "DNA_domain_or_region", "text": [ "zeta-globin mRNA cap site" ], "offsets": [ [ 1542, 1567 ] ], "normalized": [] }, { "id": "4349", "type": "RNA_molecule", "text": [ "zeta-globin mRNA" ], "offsets": [ [ 1542, 1558 ] ], "normalized": [] }, { "id": "4350", "type": "protein_family_or_group", "text": [ "zeta-globin" ], "offsets": [ [ 1542, 1553 ] ], "normalized": [] }, { "id": "4351", "type": "other_name", "text": [ "high-level promoter activity" ], "offsets": [ [ 1586, 1614 ] ], "normalized": [] }, { "id": "4352", "type": "cell_line", "text": [ "K562 cells" ], "offsets": [ [ 1618, 1628 ] ], "normalized": [] }, { "id": "4353", "type": "protein_molecule", "text": [ "GATA-1" ], "offsets": [ [ 1652, 1658 ] ], "normalized": [] }, { "id": "4354", "type": "protein_family_or_group", "text": [ "additional unknown factors" ], "offsets": [ [ 1663, 1689 ] ], "normalized": [] }, { "id": "4355", "type": "other_name", "text": [ "maximal activity" ], "offsets": [ [ 1694, 1710 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "4357", "type": "title", "text": [ "Analysis of the role of protein kinase C-alpha, -epsilon, and -zeta in T cell activation." ], "offsets": [ [ 0, 89 ] ] }, { "id": "4358", "type": "abstract", "text": [ "T cells express multiple isotypes of protein kinase C (PKC) and although it is well accepted that PKCs have an important role in T cell activation, little is known about the function of individual PKC isotypes. To address this issue, mutationally active PKC-alpha, -epsilon, or -zeta have been transfected into T cells and the consequences for T cell activation determined. p21ras plays an essential role in T cell activation. Accordingly, the effects of the constitutively active PKCs were compared to the effects of mutationally activated p21ras. The data indicate that PKC-epsilon and, to a lesser extent PKC-alpha but not -zeta, can regulate the transcription factors AP-1 and nuclear factor of activated T cells (NF-AT-1). The ability of PKC-epsilon to induce transactivation of NF-AT-1 and AP-1 was similar to the stimulatory effect of a constitutively activated p21ras. PKC-epsilon, but not PKC-alpha nor activated p21ras, was able to induce NF-KB activity. Phorbol esters induce expression of CD69 whereas none of the activated PKC isotypes tested were able to have this effect. Activated Src and p21ras were able to induce CD69 expression. These results indicate selective functions for different PKC isotypes in T cells. Moreover, the data comparing the effects of activated Ras and PKC mutants suggest that PKC-alpha, p21ras, and PKC-epsilon are not positioned linearly on a single signal transduction pathway." ], "offsets": [ [ 90, 1511 ] ] } ]

[ { "id": "4359", "type": "(AND protein_molecule protein_molecule protein_molecule)", "text": [ "protein kinase C-alpha, -epsilon, and -zeta" ], "offsets": [ [ 24, 67 ] ], "normalized": [] }, { "id": "4360", "type": "", "text": [ "protein kinase C" ], "offsets": [ [ 24, 40 ] ], "normalized": [] }, { "id": "4361", "type": "", "text": [ "-alpha" ], "offsets": [ [ 40, 46 ] ], "normalized": [] }, { "id": "4362", "type": "", "text": [ "-epsilon" ], "offsets": [ [ 48, 56 ] ], "normalized": [] }, { "id": "4363", "type": "", "text": [ "-zeta" ], "offsets": [ [ 62, 67 ] ], "normalized": [] }, { "id": "4364", "type": "other_name", "text": [ "T cell activation" ], "offsets": [ [ 71, 88 ] ], "normalized": [] }, { "id": "4365", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 90, 97 ] ], "normalized": [] }, { "id": "4366", "type": "protein_molecule", "text": [ "protein kinase C" ], "offsets": [ [ 127, 143 ] ], "normalized": [] }, { "id": "4367", "type": "protein_molecule", "text": [ "PKC" ], "offsets": [ [ 145, 148 ] ], "normalized": [] }, { "id": "4368", "type": "protein_molecule", "text": [ "PKCs" ], "offsets": [ [ 188, 192 ] ], "normalized": [] }, { "id": "4369", "type": "other_name", "text": [ "T cell activation" ], "offsets": [ [ 219, 236 ] ], "normalized": [] }, { "id": "4370", "type": "protein_family_or_group", "text": [ "PKC isotypes" ], "offsets": [ [ 287, 299 ] ], "normalized": [] }, { "id": "4371", "type": "(OR protein_molecule protein_molecule protein_molecule)", "text": [ "PKC-alpha, -epsilon, or -zeta" ], "offsets": [ [ 344, 373 ] ], "normalized": [] }, { "id": "4372", "type": "", "text": [ "PKC" ], "offsets": [ [ 344, 347 ] ], "normalized": [] }, { "id": "4373", "type": "", "text": [ "-alpha" ], "offsets": [ [ 347, 353 ] ], "normalized": [] }, { "id": "4374", "type": "", "text": [ "-epsilon" ], "offsets": [ [ 355, 363 ] ], "normalized": [] }, { "id": "4375", "type": "", "text": [ "-zeta" ], "offsets": [ [ 368, 373 ] ], "normalized": [] }, { "id": "4376", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 401, 408 ] ], "normalized": [] }, { "id": "4377", "type": "other_name", "text": [ "T cell activation" ], "offsets": [ [ 434, 451 ] ], "normalized": [] }, { "id": "4378", "type": "protein_molecule", "text": [ "p21ras" ], "offsets": [ [ 464, 470 ] ], "normalized": [] }, { "id": "4379", "type": "other_name", "text": [ "T cell activation" ], "offsets": [ [ 498, 515 ] ], "normalized": [] }, { "id": "4380", "type": "protein_family_or_group", "text": [ "constitutively active PKCs" ], "offsets": [ [ 549, 575 ] ], "normalized": [] }, { "id": "4381", "type": "protein_molecule", "text": [ "p21ras" ], "offsets": [ [ 631, 637 ] ], "normalized": [] }, { "id": "4382", "type": "protein_molecule", "text": [ "PKC-epsilon" ], "offsets": [ [ 662, 673 ] ], "normalized": [] }, { "id": "4383", "type": "protein_molecule", "text": [ "PKC-alpha" ], "offsets": [ [ 698, 707 ] ], "normalized": [] }, { "id": "4384", "type": "protein_molecule", "text": [ "-zeta" ], "offsets": [ [ 716, 721 ] ], "normalized": [] }, { "id": "4385", "type": "protein_family_or_group", "text": [ "transcription factors" ], "offsets": [ [ 740, 761 ] ], "normalized": [] }, { "id": "4386", "type": "protein_molecule", "text": [ "AP-1" ], "offsets": [ [ 762, 766 ] ], "normalized": [] }, { "id": "4387", "type": "protein_family_or_group", "text": [ "factor of activated T cells" ], "offsets": [ [ 779, 806 ] ], "normalized": [] }, { "id": "4388", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 799, 806 ] ], "normalized": [] }, { "id": "4389", "type": "protein_molecule", "text": [ "NF-AT-1" ], "offsets": [ [ 808, 815 ] ], "normalized": [] }, { "id": "4390", "type": "protein_molecule", "text": [ "PKC-epsilon" ], "offsets": [ [ 833, 844 ] ], "normalized": [] }, { "id": "4391", "type": "protein_molecule", "text": [ "NF-AT-1" ], "offsets": [ [ 874, 881 ] ], "normalized": [] }, { "id": "4392", "type": "protein_molecule", "text": [ "AP-1" ], "offsets": [ [ 886, 890 ] ], "normalized": [] }, { "id": "4393", "type": "protein_molecule", "text": [ "constitutively activated p21ras" ], "offsets": [ [ 934, 965 ] ], "normalized": [] }, { "id": "4394", "type": "protein_molecule", "text": [ "p21ras" ], "offsets": [ [ 959, 965 ] ], "normalized": [] }, { "id": "4395", "type": "protein_molecule", "text": [ "PKC-epsilon" ], "offsets": [ [ 967, 978 ] ], "normalized": [] }, { "id": "4396", "type": "protein_molecule", "text": [ "PKC-alpha" ], "offsets": [ [ 988, 997 ] ], "normalized": [] }, { "id": "4397", "type": "protein_molecule", "text": [ "p21ras" ], "offsets": [ [ 1012, 1018 ] ], "normalized": [] }, { "id": "4398", "type": "other_name", "text": [ "NF-KB activity" ], "offsets": [ [ 1039, 1053 ] ], "normalized": [] }, { "id": "4399", "type": "protein_molecule", "text": [ "NF-KB" ], "offsets": [ [ 1039, 1044 ] ], "normalized": [] }, { "id": "4400", "type": "other_organic_compound", "text": [ "Phorbol esters" ], "offsets": [ [ 1055, 1069 ] ], "normalized": [] }, { "id": "4401", "type": "protein_molecule", "text": [ "CD69" ], "offsets": [ [ 1091, 1095 ] ], "normalized": [] }, { "id": "4402", "type": "protein_family_or_group", "text": [ "activated PKC isotypes" ], "offsets": [ [ 1116, 1138 ] ], "normalized": [] }, { "id": "4403", "type": "protein_family_or_group", "text": [ "PKC isotypes" ], "offsets": [ [ 1126, 1138 ] ], "normalized": [] }, { "id": "4404", "type": "protein_family_or_group", "text": [ "Src" ], "offsets": [ [ 1187, 1190 ] ], "normalized": [] }, { "id": "4405", "type": "protein_molecule", "text": [ "p21ras" ], "offsets": [ [ 1195, 1201 ] ], "normalized": [] }, { "id": "4406", "type": "other_name", "text": [ "CD69 expression" ], "offsets": [ [ 1222, 1237 ] ], "normalized": [] }, { "id": "4407", "type": "protein_molecule", "text": [ "CD69" ], "offsets": [ [ 1222, 1226 ] ], "normalized": [] }, { "id": "4408", "type": "protein_family_or_group", "text": [ "PKC isotypes" ], "offsets": [ [ 1296, 1308 ] ], "normalized": [] }, { "id": "4409", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 1312, 1319 ] ], "normalized": [] }, { "id": "4410", "type": "protein_family_or_group", "text": [ "activated Ras" ], "offsets": [ [ 1365, 1378 ] ], "normalized": [] }, { "id": "4411", "type": "protein_family_or_group", "text": [ "PKC mutants" ], "offsets": [ [ 1383, 1394 ] ], "normalized": [] }, { "id": "4412", "type": "protein_molecule", "text": [ "PKC-alpha" ], "offsets": [ [ 1408, 1417 ] ], "normalized": [] }, { "id": "4413", "type": "protein_molecule", "text": [ "p21ras" ], "offsets": [ [ 1419, 1425 ] ], "normalized": [] }, { "id": "4414", "type": "protein_molecule", "text": [ "PKC-epsilon" ], "offsets": [ [ 1431, 1442 ] ], "normalized": [] }, { "id": "4415", "type": "other_name", "text": [ "single signal transduction pathway" ], "offsets": [ [ 1476, 1510 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "4417", "type": "title", "text": [ "Differences in binding of glucocorticoid receptor to DNA in steroid-resistant asthma." ], "offsets": [ [ 0, 85 ] ] }, { "id": "4418", "type": "abstract", "text": [ "Although glucocorticosteroids are a very effective treatment for asthma and other chronic inflammatory diseases, a small proportion of patients are resistant to their therapeutic effects. The molecular mechanism for this steroid resistance is unclear. Steroid resistance cannot be explained by pharmacokinetic mechanisms, by a defect in the binding of steroids to glucocorticoid receptors, nor by defective nuclear translocation of this receptor, thereby suggesting that the molecular abnormality lies distal to nuclear translocation. We examined the ability of nuclear translocated glucocorticoid receptors to bind to their DNA binding sites (GRE) using electrophoretic mobility shift assays in PBMC from patients with steroid-sensitive and steroid-resistant asthma. The binding of the glucocorticoid receptor to DNA in these patients was also studied using Scatchard analysis. Dexamethasone induced a significant rapid and sustained twofold increase in GRE binding in PBMCs from steroid-sensitive asthmatic patients and nonasthmatic individuals, but this was markedly reduced in steroid-resistant asthmatic patients. Scatchard analysis of glucocorticoid receptor-GRE binding showed no change in binding affinity but did show a reduced number of receptors available for DNA binding in the steroid-resistant patients. These results suggest that the ability of the glucocorticoid receptor to bind to GRE is impaired in steroid-resistant patients because of a reduced number of receptors available for binding to DNA." ], "offsets": [ [ 86, 1601 ] ] } ]

[ { "id": "4419", "type": "protein_family_or_group", "text": [ "glucocorticoid receptor" ], "offsets": [ [ 26, 49 ] ], "normalized": [] }, { "id": "4420", "type": "other_name", "text": [ "steroid-resistant asthma" ], "offsets": [ [ 60, 84 ] ], "normalized": [] }, { "id": "4421", "type": "lipid", "text": [ "glucocorticosteroids" ], "offsets": [ [ 95, 115 ] ], "normalized": [] }, { "id": "4422", "type": "other_name", "text": [ "asthma" ], "offsets": [ [ 151, 157 ] ], "normalized": [] }, { "id": "4423", "type": "other_name", "text": [ "chronic inflammatory diseases" ], "offsets": [ [ 168, 197 ] ], "normalized": [] }, { "id": "4424", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 221, 229 ] ], "normalized": [] }, { "id": "4425", "type": "other_name", "text": [ "therapeutic effects" ], "offsets": [ [ 253, 272 ] ], "normalized": [] }, { "id": "4426", "type": "other_name", "text": [ "steroid resistance" ], "offsets": [ [ 307, 325 ] ], "normalized": [] }, { "id": "4427", "type": "other_name", "text": [ "Steroid resistance" ], "offsets": [ [ 338, 356 ] ], "normalized": [] }, { "id": "4428", "type": "other_name", "text": [ "pharmacokinetic mechanisms" ], "offsets": [ [ 380, 406 ] ], "normalized": [] }, { "id": "4429", "type": "lipid", "text": [ "steroids" ], "offsets": [ [ 438, 446 ] ], "normalized": [] }, { "id": "4430", "type": "protein_family_or_group", "text": [ "glucocorticoid receptors" ], "offsets": [ [ 450, 474 ] ], "normalized": [] }, { "id": "4431", "type": "other_name", "text": [ "defective nuclear translocation" ], "offsets": [ [ 483, 514 ] ], "normalized": [] }, { "id": "4432", "type": "other_name", "text": [ "nuclear translocation" ], "offsets": [ [ 493, 514 ] ], "normalized": [] }, { "id": "4433", "type": "protein_family_or_group", "text": [ "glucocorticoid receptors" ], "offsets": [ [ 669, 693 ] ], "normalized": [] }, { "id": "4434", "type": "DNA_domain_or_region", "text": [ "DNA binding sites" ], "offsets": [ [ 711, 728 ] ], "normalized": [] }, { "id": "4435", "type": "DNA_domain_or_region", "text": [ "GRE" ], "offsets": [ [ 730, 733 ] ], "normalized": [] }, { "id": "4436", "type": "other_name", "text": [ "electrophoretic mobility shift assays" ], "offsets": [ [ 741, 778 ] ], "normalized": [] }, { "id": "4437", "type": "cell_type", "text": [ "PBMC" ], "offsets": [ [ 782, 786 ] ], "normalized": [] }, { "id": "4438", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 792, 800 ] ], "normalized": [] }, { "id": "4439", "type": "other_name", "text": [ "steroid-resistant asthma" ], "offsets": [ [ 828, 852 ] ], "normalized": [] }, { "id": "4440", "type": "other_name", "text": [ "asthma" ], "offsets": [ [ 846, 852 ] ], "normalized": [] }, { "id": "4441", "type": "protein_family_or_group", "text": [ "glucocorticoid receptor" ], "offsets": [ [ 873, 896 ] ], "normalized": [] }, { "id": "4442", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 913, 921 ] ], "normalized": [] }, { "id": "4443", "type": "other_name", "text": [ "Scatchard analysis" ], "offsets": [ [ 945, 963 ] ], "normalized": [] }, { "id": "4444", "type": "lipid", "text": [ "Dexamethasone" ], "offsets": [ [ 965, 978 ] ], "normalized": [] }, { "id": "4445", "type": "other_name", "text": [ "GRE binding" ], "offsets": [ [ 1041, 1052 ] ], "normalized": [] }, { "id": "4446", "type": "DNA_domain_or_region", "text": [ "GRE" ], "offsets": [ [ 1041, 1044 ] ], "normalized": [] }, { "id": "4447", "type": "cell_type", "text": [ "PBMCs" ], "offsets": [ [ 1056, 1061 ] ], "normalized": [] }, { "id": "4448", "type": "multi_cell", "text": [ "asthmatic patients" ], "offsets": [ [ 1085, 1103 ] ], "normalized": [] }, { "id": "4449", "type": "multi_cell", "text": [ "nonasthmatic individuals" ], "offsets": [ [ 1108, 1132 ] ], "normalized": [] }, { "id": "4450", "type": "multi_cell", "text": [ "steroid-resistant asthmatic patients" ], "offsets": [ [ 1167, 1203 ] ], "normalized": [] }, { "id": "4451", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 1095, 1103 ] ], "normalized": [] }, { "id": "4452", "type": "other_name", "text": [ "Scatchard analysis" ], "offsets": [ [ 1205, 1223 ] ], "normalized": [] }, { "id": "4453", "type": "protein_family_or_group", "text": [ "glucocorticoid receptor" ], "offsets": [ [ 1227, 1250 ] ], "normalized": [] }, { "id": "4454", "type": "other_name", "text": [ "GRE binding" ], "offsets": [ [ 1251, 1262 ] ], "normalized": [] }, { "id": "4455", "type": "DNA_domain_or_region", "text": [ "GRE" ], "offsets": [ [ 1251, 1254 ] ], "normalized": [] }, { "id": "4456", "type": "protein_family_or_group", "text": [ "receptors" ], "offsets": [ [ 1333, 1342 ] ], "normalized": [] }, { "id": "4457", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 1394, 1402 ] ], "normalized": [] }, { "id": "4458", "type": "protein_family_or_group", "text": [ "glucocorticoid receptor" ], "offsets": [ [ 1450, 1473 ] ], "normalized": [] }, { "id": "4459", "type": "DNA_domain_or_region", "text": [ "GRE" ], "offsets": [ [ 1485, 1488 ] ], "normalized": [] }, { "id": "4460", "type": "multi_cell", "text": [ "steroid-resistant patients" ], "offsets": [ [ 1504, 1530 ] ], "normalized": [] }, { "id": "4461", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 1522, 1530 ] ], "normalized": [] }, { "id": "4462", "type": "protein_family_or_group", "text": [ "receptors" ], "offsets": [ [ 1562, 1571 ] ], "normalized": [] } ]

[]

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[ { "id": "4464", "type": "title", "text": [ "Interleukin-5 signaling in human eosinophils involves JAK2 tyrosine kinase and Stat1 alpha." ], "offsets": [ [ 0, 91 ] ] }, { "id": "4465", "type": "abstract", "text": [ "Signaling by a wide variety of cytokines, including interferons, interleukins, and growth factors, involves activation of JAK kinases and Stat (Signal transducers and activators of transcription) proteins. At present, not much is known about the molecular mechanisms by which interleukin-5 (IL-5) exerts its diverse biologic effects. Human eosinophils are one of the most important target cells for IL-5 and were used here to study IL-5 signaling in a primary human cell. IL-5 induced rapid and transient tyrosine phosphorylation of JAK2. Moreover, IL-5 induced at least two DNA-binding complexes, using nuclear extracts from normal human eosinophils and the IL-6/interferon-gamma response element of the ICAM-1 promoter (ICAM-1 pIRE) in an electromobility shift assay. From supershift experiments it was concluded that one DNA-binding complex contained Stat1 alpha, probably as a homodimer. Both DNA-binding complexes were inhibited by a phosphotyrosine antibody (4G10), suggesting that tyrosine phosphorylation is required for complex formation. IL-3 and granulocyte-macrophage colony-stimulating factor induced, similar to IL-5, two DNA-binding complexes in human eosinophils, including Stat1 alpha. These data show for the first time that molecular mechanisms of IL-5 signaling in human eosinophils involve members of the JAK kinase family as well as members of the Stat family." ], "offsets": [ [ 92, 1474 ] ] } ]

[ { "id": "4466", "type": "other_name", "text": [ "Interleukin-5 signaling" ], "offsets": [ [ 0, 23 ] ], "normalized": [] }, { "id": "4467", "type": "protein_molecule", "text": [ "Interleukin-5" ], "offsets": [ [ 0, 13 ] ], "normalized": [] }, { "id": "4468", "type": "cell_type", "text": [ "human eosinophils" ], "offsets": [ [ 27, 44 ] ], "normalized": [] }, { "id": "4469", "type": "protein_molecule", "text": [ "JAK2 tyrosine kinase" ], "offsets": [ [ 54, 74 ] ], "normalized": [] }, { "id": "4470", "type": "protein_molecule", "text": [ "JAK2" ], "offsets": [ [ 54, 58 ] ], "normalized": [] }, { "id": "4471", "type": "protein_molecule", "text": [ "Stat1 alpha" ], "offsets": [ [ 79, 90 ] ], "normalized": [] }, { "id": "4472", "type": "protein_family_or_group", "text": [ "cytokines" ], "offsets": [ [ 123, 132 ] ], "normalized": [] }, { "id": "4473", "type": "protein_family_or_group", "text": [ "interferons" ], "offsets": [ [ 144, 155 ] ], "normalized": [] }, { "id": "4474", "type": "protein_family_or_group", "text": [ "interleukins" ], "offsets": [ [ 157, 169 ] ], "normalized": [] }, { "id": "4475", "type": "protein_family_or_group", "text": [ "growth factors" ], "offsets": [ [ 175, 189 ] ], "normalized": [] }, { "id": "4476", "type": "protein_family_or_group", "text": [ "JAK kinases" ], "offsets": [ [ 214, 225 ] ], "normalized": [] }, { "id": "4477", "type": "protein_family_or_group", "text": [ "Stat (Signal transducers and activators of transcription) proteins" ], "offsets": [ [ 230, 296 ] ], "normalized": [] }, { "id": "4478", "type": "protein_family_or_group", "text": [ "Stat" ], "offsets": [ [ 230, 234 ] ], "normalized": [] }, { "id": "4479", "type": "protein_family_or_group", "text": [ "Signal transducers and activators of transcription" ], "offsets": [ [ 236, 286 ] ], "normalized": [] }, { "id": "4480", "type": "protein_molecule", "text": [ "interleukin-5" ], "offsets": [ [ 368, 381 ] ], "normalized": [] }, { "id": "4481", "type": "protein_molecule", "text": [ "IL-5" ], "offsets": [ [ 383, 387 ] ], "normalized": [] }, { "id": "4482", "type": "other_name", "text": [ "diverse biologic effects" ], "offsets": [ [ 400, 424 ] ], "normalized": [] }, { "id": "4483", "type": "cell_type", "text": [ "Human eosinophils" ], "offsets": [ [ 426, 443 ] ], "normalized": [] }, { "id": "4484", "type": "cell_type", "text": [ "target cells" ], "offsets": [ [ 474, 486 ] ], "normalized": [] }, { "id": "4485", "type": "protein_molecule", "text": [ "IL-5" ], "offsets": [ [ 491, 495 ] ], "normalized": [] }, { "id": "4486", "type": "other_name", "text": [ "IL-5 signaling" ], "offsets": [ [ 524, 538 ] ], "normalized": [] }, { "id": "4487", "type": "protein_molecule", "text": [ "IL-5" ], "offsets": [ [ 524, 528 ] ], "normalized": [] }, { "id": "4488", "type": "cell_type", "text": [ "primary human cell" ], "offsets": [ [ 544, 562 ] ], "normalized": [] }, { "id": "4489", "type": "protein_molecule", "text": [ "IL-5" ], "offsets": [ [ 564, 568 ] ], "normalized": [] }, { "id": "4490", "type": "other_name", "text": [ "tyrosine phosphorylation" ], "offsets": [ [ 597, 621 ] ], "normalized": [] }, { "id": "4491", "type": "amino_acid_monomer", "text": [ "tyrosine" ], "offsets": [ [ 597, 605 ] ], "normalized": [] }, { "id": "4492", "type": "protein_molecule", "text": [ "JAK2" ], "offsets": [ [ 625, 629 ] ], "normalized": [] }, { "id": "4493", "type": "protein_molecule", "text": [ "IL-5" ], "offsets": [ [ 641, 645 ] ], "normalized": [] }, { "id": "4494", "type": "protein_complex", "text": [ "DNA-binding complexes" ], "offsets": [ [ 667, 688 ] ], "normalized": [] }, { "id": "4495", "type": "cell_component", "text": [ "nuclear extracts" ], "offsets": [ [ 696, 712 ] ], "normalized": [] }, { "id": "4496", "type": "cell_type", "text": [ "human eosinophils" ], "offsets": [ [ 725, 742 ] ], "normalized": [] }, { "id": "4497", "type": "DNA_domain_or_region", "text": [ "IL-6/interferon-gamma response element" ], "offsets": [ [ 751, 789 ] ], "normalized": [] }, { "id": "4498", "type": "DNA_domain_or_region", "text": [ "ICAM-1 promoter" ], "offsets": [ [ 797, 812 ] ], "normalized": [] }, { "id": "4499", "type": "DNA_domain_or_region", "text": [ "ICAM-1 pIRE" ], "offsets": [ [ 814, 825 ] ], "normalized": [] }, { "id": "4500", "type": "other_name", "text": [ "electromobility shift assay" ], "offsets": [ [ 833, 860 ] ], "normalized": [] }, { "id": "4501", "type": "other_name", "text": [ "supershift experiments" ], "offsets": [ [ 867, 889 ] ], "normalized": [] }, { "id": "4502", "type": "protein_complex", "text": [ "DNA-binding complex" ], "offsets": [ [ 916, 935 ] ], "normalized": [] }, { "id": "4503", "type": "protein_molecule", "text": [ "Stat1 alpha" ], "offsets": [ [ 946, 957 ] ], "normalized": [] }, { "id": "4504", "type": "protein_complex", "text": [ "DNA-binding complexes" ], "offsets": [ [ 989, 1010 ] ], "normalized": [] }, { "id": "4505", "type": "protein_family_or_group", "text": [ "phosphotyrosine antibody" ], "offsets": [ [ 1031, 1055 ] ], "normalized": [] }, { "id": "4506", "type": "protein_molecule", "text": [ "4G10" ], "offsets": [ [ 1057, 1061 ] ], "normalized": [] }, { "id": "4507", "type": "other_name", "text": [ "tyrosine phosphorylation" ], "offsets": [ [ 1080, 1104 ] ], "normalized": [] }, { "id": "4508", "type": "amino_acid_monomer", "text": [ "tyrosine" ], "offsets": [ [ 1038, 1046 ] ], "normalized": [] }, { "id": "4509", "type": "other_name", "text": [ "complex formation" ], "offsets": [ [ 1121, 1138 ] ], "normalized": [] }, { "id": "4510", "type": "protein_family_or_group", "text": [ "IL-3" ], "offsets": [ [ 1140, 1144 ] ], "normalized": [] }, { "id": "4511", "type": "protein_molecule", "text": [ "granulocyte-macrophage colony-stimulating factor" ], "offsets": [ [ 1149, 1197 ] ], "normalized": [] }, { "id": "4512", "type": "protein_molecule", "text": [ "IL-5" ], "offsets": [ [ 1218, 1222 ] ], "normalized": [] }, { "id": "4513", "type": "protein_complex", "text": [ "DNA-binding complexes" ], "offsets": [ [ 1228, 1249 ] ], "normalized": [] }, { "id": "4514", "type": "cell_type", "text": [ "human eosinophils" ], "offsets": [ [ 1253, 1270 ] ], "normalized": [] }, { "id": "4515", "type": "protein_molecule", "text": [ "Stat1 alpha" ], "offsets": [ [ 1282, 1293 ] ], "normalized": [] }, { "id": "4516", "type": "other_name", "text": [ "IL-5 signaling" ], "offsets": [ [ 1359, 1373 ] ], "normalized": [] }, { "id": "4517", "type": "protein_molecule", "text": [ "IL-5" ], "offsets": [ [ 1359, 1363 ] ], "normalized": [] }, { "id": "4518", "type": "cell_type", "text": [ "human eosinophils" ], "offsets": [ [ 1377, 1394 ] ], "normalized": [] }, { "id": "4519", "type": "protein_family_or_group", "text": [ "JAK kinase family" ], "offsets": [ [ 1418, 1435 ] ], "normalized": [] }, { "id": "4520", "type": "protein_family_or_group", "text": [ "Stat family" ], "offsets": [ [ 1462, 1473 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "4522", "type": "title", "text": [ "Infection and replication of Tat- human immunodeficiency viruses: genetic analyses of LTR and tat mutations in primary and long-term human lymphoid cells." ], "offsets": [ [ 0, 154 ] ] }, { "id": "4523", "type": "abstract", "text": [ "Tat is an essential regulatory protein for the replication of human immunodeficiency virus (HIV). Mutations in the tat gene have been shown to block HIV replication in human T cells. Several studies have established that Tat releases an elongation block to the transcription of HIV long terminal repeat (LTR); however, it is not known whether this mechanism alone is sufficient to explain the block to HIV replication in human T cells when Tat is absent. It is possible that Tat is also needed for other functions during HIV replication. To test these hypotheses, we studied several tat mutants, including two stop codon mutants and one deletion mutant using replication-competent HIV-1 constructs carrying wild-type or mutant LTRs with modifications in the NF-kappa B and/or Sp1 binding sites. In this study, we show that Tat- HIV-1 with wild-type LTRs can replicate in HeLa cells, and the virus produced from HeLa cells can infect primary peripheral blood lymphocytes and macrophages. It was found that the propagation of the Tat mutants containing wild-type LTRs was less efficient than that of the LTR-modified Tat mutants. Large amounts of viral RNA and particles were synthesized in infections established using the tat mutants that contain modified LTRs. However, this efficient propagation of the LTR-modified tat mutants was restricted to some lymphoid cell lines that have been transformed with other viruses. Thus, despite its essential role for releasing an elongation block, Tat is not otherwise absolutely required for synthesis of full-length HIV transcripts and assembly of virus particles. Direct sequencing of the viral genomes and reinfection kinetics showed no evidence of wild-type reversion even after prolonged infection with the Tat -virus. The implications for in vivo HIV-1 replication and potential application of this system to the study of alternative Tat function are discussed." ], "offsets": [ [ 155, 2063 ] ] } ]

[ { "id": "4524", "type": "virus", "text": [ "Tat- human immunodeficiency viruses" ], "offsets": [ [ 29, 64 ] ], "normalized": [] }, { "id": "4525", "type": "DNA_domain_or_region", "text": [ "LTR" ], "offsets": [ [ 86, 89 ] ], "normalized": [] }, { "id": "4526", "type": "protein_family_or_group", "text": [ "tat mutations" ], "offsets": [ [ 94, 107 ] ], "normalized": [] }, { "id": "4527", "type": "(AND cell_type cell_type)", "text": [ "primary and long-term human lymphoid cells" ], "offsets": [ [ 111, 153 ] ], "normalized": [] }, { "id": "4528", "type": "", "text": [ "primary" ], "offsets": [ [ 111, 118 ] ], "normalized": [] }, { "id": "4529", "type": "", "text": [ "long-term" ], "offsets": [ [ 123, 132 ] ], "normalized": [] }, { "id": "4530", "type": "", "text": [ "human lymphoid cells" ], "offsets": [ [ 133, 153 ] ], "normalized": [] }, { "id": "4531", "type": "protein_molecule", "text": [ "Tat" ], "offsets": [ [ 155, 158 ] ], "normalized": [] }, { "id": "4532", "type": "protein_family_or_group", "text": [ "regulatory protein" ], "offsets": [ [ 175, 193 ] ], "normalized": [] }, { "id": "4533", "type": "virus", "text": [ "human immunodeficiency virus" ], "offsets": [ [ 217, 245 ] ], "normalized": [] }, { "id": "4534", "type": "virus", "text": [ "HIV" ], "offsets": [ [ 247, 250 ] ], "normalized": [] }, { "id": "4535", "type": "DNA_domain_or_region", "text": [ "tat gene" ], "offsets": [ [ 270, 278 ] ], "normalized": [] }, { "id": "4536", "type": "other_name", "text": [ "HIV replication" ], "offsets": [ [ 304, 319 ] ], "normalized": [] }, { "id": "4537", "type": "cell_type", "text": [ "human T cells" ], "offsets": [ [ 323, 336 ] ], "normalized": [] }, { "id": "4538", "type": "protein_molecule", "text": [ "Tat" ], "offsets": [ [ 376, 379 ] ], "normalized": [] }, { "id": "4539", "type": "protein_complex", "text": [ "elongation block" ], "offsets": [ [ 392, 408 ] ], "normalized": [] }, { "id": "4540", "type": "other_name", "text": [ "transcription" ], "offsets": [ [ 416, 429 ] ], "normalized": [] }, { "id": "4541", "type": "DNA_domain_or_region", "text": [ "HIV long terminal repeat" ], "offsets": [ [ 433, 457 ] ], "normalized": [] }, { "id": "4542", "type": "DNA_domain_or_region", "text": [ "LTR" ], "offsets": [ [ 459, 462 ] ], "normalized": [] }, { "id": "4543", "type": "other_name", "text": [ "HIV replication" ], "offsets": [ [ 557, 572 ] ], "normalized": [] }, { "id": "4544", "type": "cell_type", "text": [ "human T cells" ], "offsets": [ [ 576, 589 ] ], "normalized": [] }, { "id": "4545", "type": "protein_molecule", "text": [ "Tat" ], "offsets": [ [ 595, 598 ] ], "normalized": [] }, { "id": "4546", "type": "protein_molecule", "text": [ "Tat" ], "offsets": [ [ 630, 633 ] ], "normalized": [] }, { "id": "4547", "type": "other_name", "text": [ "HIV replication" ], "offsets": [ [ 676, 691 ] ], "normalized": [] }, { "id": "4548", "type": "protein_family_or_group", "text": [ "tat mutants" ], "offsets": [ [ 738, 749 ] ], "normalized": [] }, { "id": "4549", "type": "protein_family_or_group", "text": [ "stop codon mutants" ], "offsets": [ [ 765, 783 ] ], "normalized": [] }, { "id": "4550", "type": "protein_family_or_group", "text": [ "deletion mutant" ], "offsets": [ [ 792, 807 ] ], "normalized": [] }, { "id": "4551", "type": "DNA_family_or_group", "text": [ "replication-competent HIV-1 constructs" ], "offsets": [ [ 814, 852 ] ], "normalized": [] }, { "id": "4552", "type": "(OR DNA_domain_or_region DNA_domain_or_region)", "text": [ "wild-type or mutant LTRs" ], "offsets": [ [ 862, 886 ] ], "normalized": [] }, { "id": "4553", "type": "", "text": [ "wild-type" ], "offsets": [ [ 862, 871 ] ], "normalized": [] }, { "id": "4554", "type": "", "text": [ "mutant" ], "offsets": [ [ 742, 748 ] ], "normalized": [] }, { "id": "4555", "type": "", "text": [ "LTRs" ], "offsets": [ [ 882, 886 ] ], "normalized": [] }, { "id": "4556", "type": "(AND/OR DNA_domain_or_region DNA_domain_or_region)", "text": [ "NF-kappa B and/or Sp1 binding sites" ], "offsets": [ [ 913, 948 ] ], "normalized": [] }, { "id": "4557", "type": "", "text": [ "NF-kappa B" ], "offsets": [ [ 913, 923 ] ], "normalized": [] }, { "id": "4558", "type": "", "text": [ "Sp1" ], "offsets": [ [ 931, 934 ] ], "normalized": [] }, { "id": "4559", "type": "", "text": [ "binding sites" ], "offsets": [ [ 935, 948 ] ], "normalized": [] }, { "id": "4560", "type": "virus", "text": [ "Tat- HIV-1" ], "offsets": [ [ 978, 988 ] ], "normalized": [] }, { "id": "4561", "type": "DNA_family_or_group", "text": [ "wild-type LTRs" ], "offsets": [ [ 994, 1008 ] ], "normalized": [] }, { "id": "4562", "type": "cell_line", "text": [ "HeLa cells" ], "offsets": [ [ 1026, 1036 ] ], "normalized": [] }, { "id": "4563", "type": "virus", "text": [ "virus" ], "offsets": [ [ 1046, 1051 ] ], "normalized": [] }, { "id": "4564", "type": "cell_line", "text": [ "HeLa cells" ], "offsets": [ [ 1066, 1076 ] ], "normalized": [] }, { "id": "4565", "type": "cell_type", "text": [ "peripheral blood lymphocytes" ], "offsets": [ [ 1096, 1124 ] ], "normalized": [] }, { "id": "4566", "type": "cell_type", "text": [ "macrophages" ], "offsets": [ [ 1129, 1140 ] ], "normalized": [] }, { "id": "4567", "type": "protein_family_or_group", "text": [ "Tat mutants" ], "offsets": [ [ 1183, 1194 ] ], "normalized": [] }, { "id": "4568", "type": "protein_molecule", "text": [ "Tat" ], "offsets": [ [ 1183, 1186 ] ], "normalized": [] }, { "id": "4569", "type": "DNA_family_or_group", "text": [ "wild-type LTRs" ], "offsets": [ [ 1206, 1220 ] ], "normalized": [] }, { "id": "4570", "type": "protein_family_or_group", "text": [ "LTR-modified Tat mutants" ], "offsets": [ [ 1257, 1281 ] ], "normalized": [] }, { "id": "4571", "type": "protein_molecule", "text": [ "Tat" ], "offsets": [ [ 1270, 1273 ] ], "normalized": [] }, { "id": "4572", "type": "RNA_family_or_group", "text": [ "viral RNA" ], "offsets": [ [ 1300, 1309 ] ], "normalized": [] }, { "id": "4573", "type": "other_name", "text": [ "infections" ], "offsets": [ [ 1344, 1354 ] ], "normalized": [] }, { "id": "4574", "type": "protein_family_or_group", "text": [ "tat mutants" ], "offsets": [ [ 1377, 1388 ] ], "normalized": [] }, { "id": "4575", "type": "DNA_family_or_group", "text": [ "modified LTRs" ], "offsets": [ [ 1402, 1415 ] ], "normalized": [] }, { "id": "4576", "type": "protein_family_or_group", "text": [ "LTR-modified tat mutants" ], "offsets": [ [ 1460, 1484 ] ], "normalized": [] }, { "id": "4577", "type": "protein_family_or_group", "text": [ "tat mutants" ], "offsets": [ [ 1473, 1484 ] ], "normalized": [] }, { "id": "4578", "type": "cell_line", "text": [ "lymphoid cell lines" ], "offsets": [ [ 1508, 1527 ] ], "normalized": [] }, { "id": "4579", "type": "virus", "text": [ "viruses" ], "offsets": [ [ 1566, 1573 ] ], "normalized": [] }, { "id": "4580", "type": "protein_complex", "text": [ "elongation block" ], "offsets": [ [ 1625, 1641 ] ], "normalized": [] }, { "id": "4581", "type": "protein_molecule", "text": [ "Tat" ], "offsets": [ [ 1643, 1646 ] ], "normalized": [] }, { "id": "4582", "type": "RNA_family_or_group", "text": [ "full-length HIV transcripts" ], "offsets": [ [ 1701, 1728 ] ], "normalized": [] }, { "id": "4583", "type": "virus", "text": [ "virus particles" ], "offsets": [ [ 1745, 1760 ] ], "normalized": [] }, { "id": "4584", "type": "DNA_family_or_group", "text": [ "viral genomes" ], "offsets": [ [ 1787, 1800 ] ], "normalized": [] }, { "id": "4585", "type": "other_name", "text": [ "wild-type reversion" ], "offsets": [ [ 1848, 1867 ] ], "normalized": [] }, { "id": "4586", "type": "virus", "text": [ "Tat -virus" ], "offsets": [ [ 1908, 1918 ] ], "normalized": [] }, { "id": "4587", "type": "protein_molecule", "text": [ "Tat" ], "offsets": [ [ 1908, 1911 ] ], "normalized": [] }, { "id": "4588", "type": "other_name", "text": [ "in vivo HIV-1 replication" ], "offsets": [ [ 1941, 1966 ] ], "normalized": [] }, { "id": "4589", "type": "virus", "text": [ "HIV-1" ], "offsets": [ [ 1949, 1954 ] ], "normalized": [] }, { "id": "4590", "type": "other_name", "text": [ "Tat function" ], "offsets": [ [ 2036, 2048 ] ], "normalized": [] }, { "id": "4591", "type": "protein_molecule", "text": [ "Tat" ], "offsets": [ [ 2036, 2039 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "4593", "type": "title", "text": [ "Functional roles of the transcription factor Oct-2A and the high mobility group protein I/Y in HLA-DRA gene expression." ], "offsets": [ [ 0, 119 ] ] }, { "id": "4594", "type": "abstract", "text": [ "The class II major histocompatibility complex gene HLA-DRA is expressed in B cells, activated T lymphocytes, and in antigen-presenting cells. In addition, HLA-DRA gene expression is inducible in a variety of cell types by interferon-gamma (IFN-gamma). Here we show that the lymphoid-specific transcription factor Oct-2A plays a critical role in HLA-DRA gene expression in class II-positive B cell lines, and that the high mobility group protein (HMG) I/Y binds to multiple sites within the DRA promoter, including the Oct-2A binding site. Coexpression of HMG I/Y and Oct-2 in cell lines lacking Oct-2 results in high levels of HLA-DRA gene expression, and in vitro DNA-binding studies reveal that HMG I/Y stimulates Oct-2A binding to the HLA-DRA promoter. Thus, Oct-2A and HMG I/Y may synergize to activate HLA-DRA expression in B cells. By contrast, Oct-2A is not involved in the IFN-gamma induction of the HLA-DRA gene in HeLa cells, but antisense HMG I/Y dramatically decreases the level of induction. We conclude that distinct sets of transcription factors are involved in the two modes of HLA-DRA expression, and that HMG I/Y may be important for B cell-specific expression, and is essential for IFN-gamma induction." ], "offsets": [ [ 120, 1341 ] ] } ]

[ { "id": "4595", "type": "protein_molecule", "text": [ "transcription factor Oct-2A" ], "offsets": [ [ 24, 51 ] ], "normalized": [] }, { "id": "4596", "type": "protein_molecule", "text": [ "Oct-2A" ], "offsets": [ [ 45, 51 ] ], "normalized": [] }, { "id": "4597", "type": "protein_family_or_group", "text": [ "high mobility group protein" ], "offsets": [ [ 60, 87 ] ], "normalized": [] }, { "id": "4598", "type": "protein_molecule", "text": [ "I/Y" ], "offsets": [ [ 88, 91 ] ], "normalized": [] }, { "id": "4599", "type": "other_name", "text": [ "HLA-DRA gene expression" ], "offsets": [ [ 95, 118 ] ], "normalized": [] }, { "id": "4600", "type": "DNA_domain_or_region", "text": [ "HLA-DRA gene" ], "offsets": [ [ 95, 107 ] ], "normalized": [] }, { "id": "4601", "type": "DNA_domain_or_region", "text": [ "class II major histocompatibility complex gene" ], "offsets": [ [ 124, 170 ] ], "normalized": [] }, { "id": "4602", "type": "protein_complex", "text": [ "class II major histocompatibility complex" ], "offsets": [ [ 124, 165 ] ], "normalized": [] }, { "id": "4603", "type": "DNA_domain_or_region", "text": [ "HLA-DRA" ], "offsets": [ [ 171, 178 ] ], "normalized": [] }, { "id": "4604", "type": "cell_type", "text": [ "B cells" ], "offsets": [ [ 195, 202 ] ], "normalized": [] }, { "id": "4605", "type": "cell_type", "text": [ "T lymphocytes" ], "offsets": [ [ 214, 227 ] ], "normalized": [] }, { "id": "4606", "type": "cell_type", "text": [ "antigen-presenting cells" ], "offsets": [ [ 236, 260 ] ], "normalized": [] }, { "id": "4607", "type": "other_name", "text": [ "HLA-DRA gene expression" ], "offsets": [ [ 275, 298 ] ], "normalized": [] }, { "id": "4608", "type": "DNA_domain_or_region", "text": [ "HLA-DRA gene" ], "offsets": [ [ 275, 287 ] ], "normalized": [] }, { "id": "4609", "type": "protein_molecule", "text": [ "interferon-gamma" ], "offsets": [ [ 342, 358 ] ], "normalized": [] }, { "id": "4610", "type": "protein_molecule", "text": [ "IFN-gamma" ], "offsets": [ [ 360, 369 ] ], "normalized": [] }, { "id": "4611", "type": "protein_molecule", "text": [ "lymphoid-specific transcription factor Oct-2A" ], "offsets": [ [ 394, 439 ] ], "normalized": [] }, { "id": "4612", "type": "protein_family_or_group", "text": [ "lymphoid-specific transcription factor" ], "offsets": [ [ 394, 432 ] ], "normalized": [] }, { "id": "4613", "type": "protein_molecule", "text": [ "Oct-2A" ], "offsets": [ [ 433, 439 ] ], "normalized": [] }, { "id": "4614", "type": "other_name", "text": [ "HLA-DRA gene expression" ], "offsets": [ [ 465, 488 ] ], "normalized": [] }, { "id": "4615", "type": "DNA_domain_or_region", "text": [ "HLA-DRA gene" ], "offsets": [ [ 465, 477 ] ], "normalized": [] }, { "id": "4616", "type": "cell_line", "text": [ "class II-positive B cell lines" ], "offsets": [ [ 492, 522 ] ], "normalized": [] }, { "id": "4617", "type": "protein_family_or_group", "text": [ "high mobility group protein" ], "offsets": [ [ 537, 564 ] ], "normalized": [] }, { "id": "4618", "type": "protein_family_or_group", "text": [ "HMG" ], "offsets": [ [ 566, 569 ] ], "normalized": [] }, { "id": "4619", "type": "protein_molecule", "text": [ "I/Y" ], "offsets": [ [ 571, 574 ] ], "normalized": [] }, { "id": "4620", "type": "DNA_domain_or_region", "text": [ "DRA promoter" ], "offsets": [ [ 610, 622 ] ], "normalized": [] }, { "id": "4621", "type": "DNA_domain_or_region", "text": [ "Oct-2A binding site" ], "offsets": [ [ 638, 657 ] ], "normalized": [] }, { "id": "4622", "type": "protein_molecule", "text": [ "Oct-2A" ], "offsets": [ [ 638, 644 ] ], "normalized": [] }, { "id": "4623", "type": "protein_molecule", "text": [ "HMG I/Y" ], "offsets": [ [ 675, 682 ] ], "normalized": [] }, { "id": "4624", "type": "protein_molecule", "text": [ "I/Y" ], "offsets": [ [ 679, 682 ] ], "normalized": [] }, { "id": "4625", "type": "protein_family_or_group", "text": [ "Oct-2" ], "offsets": [ [ 687, 692 ] ], "normalized": [] }, { "id": "4626", "type": "cell_line", "text": [ "cell lines" ], "offsets": [ [ 696, 706 ] ], "normalized": [] }, { "id": "4627", "type": "protein_family_or_group", "text": [ "Oct-2" ], "offsets": [ [ 715, 720 ] ], "normalized": [] }, { "id": "4628", "type": "other_name", "text": [ "HLA-DRA gene expression" ], "offsets": [ [ 747, 770 ] ], "normalized": [] }, { "id": "4629", "type": "DNA_domain_or_region", "text": [ "HLA-DRA gene" ], "offsets": [ [ 747, 759 ] ], "normalized": [] }, { "id": "4630", "type": "protein_molecule", "text": [ "I/Y" ], "offsets": [ [ 821, 824 ] ], "normalized": [] }, { "id": "4631", "type": "other_name", "text": [ "Oct-2A binding" ], "offsets": [ [ 836, 850 ] ], "normalized": [] }, { "id": "4632", "type": "protein_molecule", "text": [ "Oct-2A" ], "offsets": [ [ 836, 842 ] ], "normalized": [] }, { "id": "4633", "type": "DNA_domain_or_region", "text": [ "HLA-DRA promoter" ], "offsets": [ [ 858, 874 ] ], "normalized": [] }, { "id": "4634", "type": "protein_molecule", "text": [ "Oct-2A" ], "offsets": [ [ 882, 888 ] ], "normalized": [] }, { "id": "4635", "type": "protein_molecule", "text": [ "HMG I/Y" ], "offsets": [ [ 893, 900 ] ], "normalized": [] }, { "id": "4636", "type": "protein_molecule", "text": [ "I/Y" ], "offsets": [ [ 897, 900 ] ], "normalized": [] }, { "id": "4637", "type": "other_name", "text": [ "HLA-DRA expression" ], "offsets": [ [ 927, 945 ] ], "normalized": [] }, { "id": "4638", "type": "DNA_domain_or_region", "text": [ "HLA-DRA" ], "offsets": [ [ 927, 934 ] ], "normalized": [] }, { "id": "4639", "type": "cell_type", "text": [ "B cells" ], "offsets": [ [ 949, 956 ] ], "normalized": [] }, { "id": "4640", "type": "protein_molecule", "text": [ "Oct-2A" ], "offsets": [ [ 971, 977 ] ], "normalized": [] }, { "id": "4641", "type": "other_name", "text": [ "IFN-gamma induction" ], "offsets": [ [ 1001, 1020 ] ], "normalized": [] }, { "id": "4642", "type": "protein_molecule", "text": [ "IFN-gamma" ], "offsets": [ [ 1001, 1010 ] ], "normalized": [] }, { "id": "4643", "type": "DNA_domain_or_region", "text": [ "HLA-DRA gene" ], "offsets": [ [ 1028, 1040 ] ], "normalized": [] }, { "id": "4644", "type": "cell_line", "text": [ "HeLa cells" ], "offsets": [ [ 1044, 1054 ] ], "normalized": [] }, { "id": "4645", "type": "DNA_molecule", "text": [ "antisense HMG I/Y" ], "offsets": [ [ 1060, 1077 ] ], "normalized": [] }, { "id": "4646", "type": "protein_molecule", "text": [ "HMG I/Y" ], "offsets": [ [ 1070, 1077 ] ], "normalized": [] }, { "id": "4647", "type": "protein_molecule", "text": [ "I/Y" ], "offsets": [ [ 1074, 1077 ] ], "normalized": [] }, { "id": "4648", "type": "protein_family_or_group", "text": [ "transcription factors" ], "offsets": [ [ 1159, 1180 ] ], "normalized": [] }, { "id": "4649", "type": "other_name", "text": [ "HLA-DRA expression" ], "offsets": [ [ 1214, 1232 ] ], "normalized": [] }, { "id": "4650", "type": "DNA_domain_or_region", "text": [ "HLA-DRA" ], "offsets": [ [ 1214, 1221 ] ], "normalized": [] }, { "id": "4651", "type": "protein_molecule", "text": [ "HMG I/Y" ], "offsets": [ [ 1243, 1250 ] ], "normalized": [] }, { "id": "4652", "type": "other_name", "text": [ "B cell-specific expression" ], "offsets": [ [ 1272, 1298 ] ], "normalized": [] }, { "id": "4653", "type": "other_name", "text": [ "IFN-gamma induction" ], "offsets": [ [ 1321, 1340 ] ], "normalized": [] }, { "id": "4654", "type": "protein_molecule", "text": [ "IFN-gamma" ], "offsets": [ [ 1321, 1330 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "4656", "type": "title", "text": [ "Heterogeneous expression of Epstein-Barr virus latent proteins in endemic Burkitt's lymphoma." ], "offsets": [ [ 0, 93 ] ] }, { "id": "4657", "type": "abstract", "text": [ "Epstein-Barr virus (EBV)-infected cells may sustain three distinct forms of virus latency. In lymphoblastoid cell lines, six EBV-encoded nuclear antigens (EBNA1, 2, 3A, 3B, 3C, -LP), three latent membrane proteins (LMP1, 2A, 2B), and two nuclear RNAs (EBERs) are expressed. This form of latency, termed latency III, is also encountered in some posttransplant lymphoproliferative disorders. In EBV-positive cases of Hodgkin's disease, the EBERs, EBNA1, and the LMPs are expressed (latency II), whereas in Burkitt's lymphoma (BL) only the EBERs and EBNA1 have been detected (latency I). We have studied the expression of EBV proteins in 17 cases of EBV-positive endemic BL by immunohistology. Expression of LMP1 was seen in variable proportions of tumor cells in two cases and EBNA2 was detected in some tumor cells in three other cases. Also, the BZLF1 trans-activator protein was expressed in a few tumor cells in 6 cases, indicating entry into the lytic cycle. A phenotypic drift from latency I to latency III has been observed previously in some BL cell lines. Our results suggest that a similar phenomenon may occur in BL in vivo and indicate that the operational definition of EBV latencies is not easily applied to human tumors." ], "offsets": [ [ 94, 1327 ] ] } ]

[ { "id": "4658", "type": "other_name", "text": [ "Heterogeneous expression" ], "offsets": [ [ 0, 24 ] ], "normalized": [] }, { "id": "4659", "type": "protein_family_or_group", "text": [ "Epstein-Barr virus latent proteins" ], "offsets": [ [ 28, 62 ] ], "normalized": [] }, { "id": "4660", "type": "virus", "text": [ "Epstein-Barr virus" ], "offsets": [ [ 28, 46 ] ], "normalized": [] }, { "id": "4661", "type": "other_name", "text": [ "Burkitt's lymphoma" ], "offsets": [ [ 74, 92 ] ], "normalized": [] }, { "id": "4662", "type": "cell_type", "text": [ "Epstein-Barr virus (EBV)-infected cells" ], "offsets": [ [ 94, 133 ] ], "normalized": [] }, { "id": "4663", "type": "virus", "text": [ "Epstein-Barr virus" ], "offsets": [ [ 94, 112 ] ], "normalized": [] }, { "id": "4664", "type": "other_name", "text": [ "virus latency" ], "offsets": [ [ 170, 183 ] ], "normalized": [] }, { "id": "4665", "type": "cell_line", "text": [ "lymphoblastoid cell lines" ], "offsets": [ [ 188, 213 ] ], "normalized": [] }, { "id": "4666", "type": "protein_molecule", "text": [ "EBV-encoded nuclear antigens" ], "offsets": [ [ 219, 247 ] ], "normalized": [] }, { "id": "4667", "type": "(AND protein_molecule protein_molecule protein_molecule protein_molecule protein_molecule protein_molecule)", "text": [ "EBNA1, 2, 3A, 3B, 3C, -LP" ], "offsets": [ [ 249, 274 ] ], "normalized": [] }, { "id": "4668", "type": "", "text": [ "EBNA" ], "offsets": [ [ 249, 253 ] ], "normalized": [] }, { "id": "4669", "type": "", "text": [ "1" ], "offsets": [ [ 253, 254 ] ], "normalized": [] }, { "id": "4670", "type": "", "text": [ "2" ], "offsets": [ [ 256, 257 ] ], "normalized": [] }, { "id": "4671", "type": "", "text": [ "3A" ], "offsets": [ [ 259, 261 ] ], "normalized": [] }, { "id": "4672", "type": "", "text": [ "3B" ], "offsets": [ [ 263, 265 ] ], "normalized": [] }, { "id": "4673", "type": "", "text": [ "3C" ], "offsets": [ [ 267, 269 ] ], "normalized": [] }, { "id": "4674", "type": "", "text": [ "-LP" ], "offsets": [ [ 271, 274 ] ], "normalized": [] }, { "id": "4675", "type": "protein_family_or_group", "text": [ "latent membrane proteins" ], "offsets": [ [ 283, 307 ] ], "normalized": [] }, { "id": "4676", "type": "protein_molecule", "text": [ "LMP1" ], "offsets": [ [ 309, 313 ] ], "normalized": [] }, { "id": "4677", "type": "protein_molecule", "text": [ "2A" ], "offsets": [ [ 315, 317 ] ], "normalized": [] }, { "id": "4678", "type": "protein_molecule", "text": [ "2B" ], "offsets": [ [ 319, 321 ] ], "normalized": [] }, { "id": "4679", "type": "RNA_family_or_group", "text": [ "nuclear RNAs" ], "offsets": [ [ 332, 344 ] ], "normalized": [] }, { "id": "4680", "type": "RNA_family_or_group", "text": [ "EBERs" ], "offsets": [ [ 346, 351 ] ], "normalized": [] }, { "id": "4681", "type": "other_name", "text": [ "latency" ], "offsets": [ [ 381, 388 ] ], "normalized": [] }, { "id": "4682", "type": "other_name", "text": [ "latency III" ], "offsets": [ [ 397, 408 ] ], "normalized": [] }, { "id": "4683", "type": "other_name", "text": [ "posttransplant lymphoproliferative disorders" ], "offsets": [ [ 438, 482 ] ], "normalized": [] }, { "id": "4684", "type": "multi_cell", "text": [ "EBV-positive cases" ], "offsets": [ [ 487, 505 ] ], "normalized": [] }, { "id": "4685", "type": "other_name", "text": [ "Hodgkin's disease" ], "offsets": [ [ 509, 526 ] ], "normalized": [] }, { "id": "4686", "type": "RNA_family_or_group", "text": [ "EBERs" ], "offsets": [ [ 532, 537 ] ], "normalized": [] }, { "id": "4687", "type": "protein_molecule", "text": [ "EBNA1" ], "offsets": [ [ 539, 544 ] ], "normalized": [] }, { "id": "4688", "type": "protein_family_or_group", "text": [ "LMPs" ], "offsets": [ [ 554, 558 ] ], "normalized": [] }, { "id": "4689", "type": "other_name", "text": [ "latency II" ], "offsets": [ [ 574, 584 ] ], "normalized": [] }, { "id": "4690", "type": "other_name", "text": [ "Burkitt's lymphoma" ], "offsets": [ [ 598, 616 ] ], "normalized": [] }, { "id": "4691", "type": "RNA_family_or_group", "text": [ "EBERs" ], "offsets": [ [ 631, 636 ] ], "normalized": [] }, { "id": "4692", "type": "protein_molecule", "text": [ "EBNA1" ], "offsets": [ [ 641, 646 ] ], "normalized": [] }, { "id": "4693", "type": "other_name", "text": [ "latency I" ], "offsets": [ [ 574, 583 ] ], "normalized": [] }, { "id": "4694", "type": "protein_family_or_group", "text": [ "EBV proteins" ], "offsets": [ [ 713, 725 ] ], "normalized": [] }, { "id": "4695", "type": "other_name", "text": [ "EBV-positive endemic BL" ], "offsets": [ [ 741, 764 ] ], "normalized": [] }, { "id": "4696", "type": "other_name", "text": [ "immunohistology" ], "offsets": [ [ 768, 783 ] ], "normalized": [] }, { "id": "4697", "type": "protein_molecule", "text": [ "LMP1" ], "offsets": [ [ 799, 803 ] ], "normalized": [] }, { "id": "4698", "type": "cell_type", "text": [ "tumor cells" ], "offsets": [ [ 840, 851 ] ], "normalized": [] }, { "id": "4699", "type": "protein_molecule", "text": [ "EBNA2" ], "offsets": [ [ 869, 874 ] ], "normalized": [] }, { "id": "4700", "type": "cell_type", "text": [ "tumor cells" ], "offsets": [ [ 896, 907 ] ], "normalized": [] }, { "id": "4701", "type": "protein_molecule", "text": [ "BZLF1 trans-activator protein" ], "offsets": [ [ 940, 969 ] ], "normalized": [] }, { "id": "4702", "type": "cell_type", "text": [ "tumor cells" ], "offsets": [ [ 993, 1004 ] ], "normalized": [] }, { "id": "4703", "type": "other_name", "text": [ "lytic cycle" ], "offsets": [ [ 1043, 1054 ] ], "normalized": [] }, { "id": "4704", "type": "other_name", "text": [ "latency I" ], "offsets": [ [ 1080, 1089 ] ], "normalized": [] }, { "id": "4705", "type": "other_name", "text": [ "latency III" ], "offsets": [ [ 1093, 1104 ] ], "normalized": [] }, { "id": "4706", "type": "cell_line", "text": [ "BL cell lines" ], "offsets": [ [ 1142, 1155 ] ], "normalized": [] }, { "id": "4707", "type": "other_name", "text": [ "BL" ], "offsets": [ [ 1216, 1218 ] ], "normalized": [] }, { "id": "4708", "type": "other_name", "text": [ "EBV latencies" ], "offsets": [ [ 1275, 1288 ] ], "normalized": [] }, { "id": "4709", "type": "tissue", "text": [ "human tumors" ], "offsets": [ [ 1314, 1326 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "4711", "type": "title", "text": [ "The activation of the Jak-STAT 1 signaling pathway by IL-5 in eosinophils." ], "offsets": [ [ 0, 74 ] ] }, { "id": "4712", "type": "abstract", "text": [ "The intracellular signal transduction of IL-5 in eosinophils is unknown. The objective of this study was to investigate the involvement of the newly discovered Jak-STAT pathway in the IL-5 signal transduction mechanism. Eosinophils were purified from peripheral blood by discontinuous Percoll gradients and stimulated with IL-5. The involvement of Jak 2 was investigated by immunoprecipitation followed by immunoblotting for tyrosine phosphorylation. The activation of Jak 2 was studied by autophosphorylation of the immunoprecipitated kinase. Jak 2 was tyrosine phosphorylated within 1 to 3 min after stimulation of eosinophils with IL-5. Further, the immunoprecipitated Jak 2 obtained from IL-5-stimulated cells underwent autophosphorylation. Jak 2 coprecipitated with the beta-subunit of the IL-5 receptor, suggesting a physical association of the kinase with the receptor. The nuclear factor STAT-1 (p91) was investigated by immunoprecipitation followed by immunoblotting for tyrosine phosphorylation. STAT-1 was tyrosine phosphorylated within 15 min of IL-5 stimulation. The presence of STAT-1 in the nuclear extract was studied by electrophoretic mobility shift assay. IL-5 induced two proteins that bound to the gamma-activating sequence. In the presence of an anti-STAT-1 Ab, the band was supershifted. Thus, we demonstrated that IL-5 activated the Jak 2-STAT 1 signaling pathway in eosinophils. We speculate that the Jak 2-STAT 1 pathway may be involved in the activation of IL-5-inducible genes in eosinophils." ], "offsets": [ [ 75, 1595 ] ] } ]

[ { "id": "4713", "type": "other_name", "text": [ "Jak-STAT 1 signaling pathway" ], "offsets": [ [ 22, 50 ] ], "normalized": [] }, { "id": "4714", "type": "protein_family_or_group", "text": [ "Jak" ], "offsets": [ [ 22, 25 ] ], "normalized": [] }, { "id": "4715", "type": "protein_molecule", "text": [ "-STAT 1" ], "offsets": [ [ 25, 32 ] ], "normalized": [] }, { "id": "4716", "type": "protein_molecule", "text": [ "IL-5" ], "offsets": [ [ 54, 58 ] ], "normalized": [] }, { "id": "4717", "type": "cell_type", "text": [ "eosinophils" ], "offsets": [ [ 62, 73 ] ], "normalized": [] }, { "id": "4718", "type": "protein_molecule", "text": [ "IL-5" ], "offsets": [ [ 116, 120 ] ], "normalized": [] }, { "id": "4719", "type": "cell_type", "text": [ "eosinophils" ], "offsets": [ [ 124, 135 ] ], "normalized": [] }, { "id": "4720", "type": "other_name", "text": [ "Jak-STAT pathway" ], "offsets": [ [ 235, 251 ] ], "normalized": [] }, { "id": "4721", "type": "protein_family_or_group", "text": [ "Jak" ], "offsets": [ [ 235, 238 ] ], "normalized": [] }, { "id": "4722", "type": "protein_family_or_group", "text": [ "-STAT" ], "offsets": [ [ 238, 243 ] ], "normalized": [] }, { "id": "4723", "type": "other_name", "text": [ "IL-5 signal transduction mechanism" ], "offsets": [ [ 259, 293 ] ], "normalized": [] }, { "id": "4724", "type": "protein_molecule", "text": [ "IL-5" ], "offsets": [ [ 259, 263 ] ], "normalized": [] }, { "id": "4725", "type": "cell_type", "text": [ "Eosinophils" ], "offsets": [ [ 295, 306 ] ], "normalized": [] }, { "id": "4726", "type": "tissue", "text": [ "peripheral blood" ], "offsets": [ [ 326, 342 ] ], "normalized": [] }, { "id": "4727", "type": "other_name", "text": [ "Percoll gradients" ], "offsets": [ [ 360, 377 ] ], "normalized": [] }, { "id": "4728", "type": "protein_molecule", "text": [ "IL-5" ], "offsets": [ [ 398, 402 ] ], "normalized": [] }, { "id": "4729", "type": "protein_family_or_group", "text": [ "Jak 2" ], "offsets": [ [ 423, 428 ] ], "normalized": [] }, { "id": "4730", "type": "other_name", "text": [ "immunoprecipitation" ], "offsets": [ [ 449, 468 ] ], "normalized": [] }, { "id": "4731", "type": "other_name", "text": [ "immunoblotting" ], "offsets": [ [ 481, 495 ] ], "normalized": [] }, { "id": "4732", "type": "other_name", "text": [ "tyrosine phosphorylation" ], "offsets": [ [ 500, 524 ] ], "normalized": [] }, { "id": "4733", "type": "amino_acid_monomer", "text": [ "tyrosine" ], "offsets": [ [ 500, 508 ] ], "normalized": [] }, { "id": "4734", "type": "protein_family_or_group", "text": [ "Jak 2" ], "offsets": [ [ 544, 549 ] ], "normalized": [] }, { "id": "4735", "type": "other_name", "text": [ "autophosphorylation" ], "offsets": [ [ 565, 584 ] ], "normalized": [] }, { "id": "4736", "type": "protein_domain_or_region", "text": [ "immunoprecipitated kinase" ], "offsets": [ [ 592, 617 ] ], "normalized": [] }, { "id": "4737", "type": "protein_family_or_group", "text": [ "Jak 2" ], "offsets": [ [ 619, 624 ] ], "normalized": [] }, { "id": "4738", "type": "other_name", "text": [ "tyrosine phosphorylated" ], "offsets": [ [ 629, 652 ] ], "normalized": [] }, { "id": "4739", "type": "amino_acid_monomer", "text": [ "tyrosine" ], "offsets": [ [ 629, 637 ] ], "normalized": [] }, { "id": "4740", "type": "cell_type", "text": [ "eosinophils" ], "offsets": [ [ 692, 703 ] ], "normalized": [] }, { "id": "4741", "type": "protein_molecule", "text": [ "IL-5" ], "offsets": [ [ 709, 713 ] ], "normalized": [] }, { "id": "4742", "type": "protein_molecule", "text": [ "immunoprecipitated Jak 2" ], "offsets": [ [ 728, 752 ] ], "normalized": [] }, { "id": "4743", "type": "protein_family_or_group", "text": [ "Jak 2" ], "offsets": [ [ 747, 752 ] ], "normalized": [] }, { "id": "4744", "type": "cell_line", "text": [ "IL-5-stimulated cells" ], "offsets": [ [ 767, 788 ] ], "normalized": [] }, { "id": "4745", "type": "protein_molecule", "text": [ "IL-5" ], "offsets": [ [ 767, 771 ] ], "normalized": [] }, { "id": "4746", "type": "other_name", "text": [ "autophosphorylation" ], "offsets": [ [ 799, 818 ] ], "normalized": [] }, { "id": "4747", "type": "protein_family_or_group", "text": [ "Jak 2" ], "offsets": [ [ 820, 825 ] ], "normalized": [] }, { "id": "4748", "type": "protein_family_or_group", "text": [ "IL-5 receptor" ], "offsets": [ [ 870, 883 ] ], "normalized": [] }, { "id": "4749", "type": "protein_molecule", "text": [ "IL-5" ], "offsets": [ [ 870, 874 ] ], "normalized": [] }, { "id": "4750", "type": "protein_family_or_group", "text": [ "kinase" ], "offsets": [ [ 926, 932 ] ], "normalized": [] }, { "id": "4751", "type": "protein_molecule", "text": [ "nuclear factor STAT-1" ], "offsets": [ [ 956, 977 ] ], "normalized": [] }, { "id": "4752", "type": "protein_molecule", "text": [ "p91" ], "offsets": [ [ 979, 982 ] ], "normalized": [] }, { "id": "4753", "type": "other_name", "text": [ "immunoprecipitation" ], "offsets": [ [ 1004, 1023 ] ], "normalized": [] }, { "id": "4754", "type": "other_name", "text": [ "immunoblotting" ], "offsets": [ [ 1036, 1050 ] ], "normalized": [] }, { "id": "4755", "type": "other_name", "text": [ "tyrosine phosphorylation" ], "offsets": [ [ 1055, 1079 ] ], "normalized": [] }, { "id": "4756", "type": "amino_acid_monomer", "text": [ "tyrosine" ], "offsets": [ [ 1055, 1063 ] ], "normalized": [] }, { "id": "4757", "type": "protein_molecule", "text": [ "STAT-1" ], "offsets": [ [ 1081, 1087 ] ], "normalized": [] }, { "id": "4758", "type": "other_name", "text": [ "tyrosine phosphorylated" ], "offsets": [ [ 1092, 1115 ] ], "normalized": [] }, { "id": "4759", "type": "amino_acid_monomer", "text": [ "tyrosine" ], "offsets": [ [ 1092, 1100 ] ], "normalized": [] }, { "id": "4760", "type": "other_name", "text": [ "IL-5 stimulation" ], "offsets": [ [ 1133, 1149 ] ], "normalized": [] }, { "id": "4761", "type": "protein_molecule", "text": [ "IL-5" ], "offsets": [ [ 1133, 1137 ] ], "normalized": [] }, { "id": "4762", "type": "protein_molecule", "text": [ "STAT-1" ], "offsets": [ [ 1167, 1173 ] ], "normalized": [] }, { "id": "4763", "type": "cell_component", "text": [ "nuclear extract" ], "offsets": [ [ 1181, 1196 ] ], "normalized": [] }, { "id": "4764", "type": "other_name", "text": [ "electrophoretic mobility shift assay" ], "offsets": [ [ 1212, 1248 ] ], "normalized": [] }, { "id": "4765", "type": "protein_molecule", "text": [ "IL-5" ], "offsets": [ [ 1250, 1254 ] ], "normalized": [] }, { "id": "4766", "type": "DNA_domain_or_region", "text": [ "gamma-activating sequence" ], "offsets": [ [ 1294, 1319 ] ], "normalized": [] }, { "id": "4767", "type": "protein_family_or_group", "text": [ "anti-STAT-1 Ab" ], "offsets": [ [ 1343, 1357 ] ], "normalized": [] }, { "id": "4768", "type": "protein_molecule", "text": [ "STAT-1" ], "offsets": [ [ 1348, 1354 ] ], "normalized": [] }, { "id": "4769", "type": "protein_molecule", "text": [ "IL-5" ], "offsets": [ [ 1413, 1417 ] ], "normalized": [] }, { "id": "4770", "type": "other_name", "text": [ "Jak 2-STAT 1 signaling pathway" ], "offsets": [ [ 1432, 1462 ] ], "normalized": [] }, { "id": "4771", "type": "protein_family_or_group", "text": [ "Jak 2" ], "offsets": [ [ 1432, 1437 ] ], "normalized": [] }, { "id": "4772", "type": "protein_molecule", "text": [ "-STAT 1" ], "offsets": [ [ 1437, 1444 ] ], "normalized": [] }, { "id": "4773", "type": "cell_type", "text": [ "eosinophils" ], "offsets": [ [ 1466, 1477 ] ], "normalized": [] }, { "id": "4774", "type": "other_name", "text": [ "Jak 2-STAT 1 pathway" ], "offsets": [ [ 1501, 1521 ] ], "normalized": [] }, { "id": "4775", "type": "protein_family_or_group", "text": [ "Jak 2" ], "offsets": [ [ 1501, 1506 ] ], "normalized": [] }, { "id": "4776", "type": "protein_molecule", "text": [ "-STAT 1" ], "offsets": [ [ 1506, 1513 ] ], "normalized": [] }, { "id": "4777", "type": "DNA_family_or_group", "text": [ "IL-5-inducible genes" ], "offsets": [ [ 1559, 1579 ] ], "normalized": [] }, { "id": "4778", "type": "protein_molecule", "text": [ "IL-5" ], "offsets": [ [ 1559, 1563 ] ], "normalized": [] }, { "id": "4779", "type": "cell_type", "text": [ "eosinophils" ], "offsets": [ [ 1583, 1594 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "4781", "type": "title", "text": [ "Reduced mitogenic stimulation of peripheral blood mononuclear cells as a prognostic parameter for the course of breast cancer: a prospective longitudinal study." ], "offsets": [ [ 0, 160 ] ] }, { "id": "4782", "type": "abstract", "text": [ "Immunosuppression has been often associated with the course of malignant diseases. In the present study, the proliferation of peripheral blood mononuclear cells (PBMCs) in response to mitogenic stimulation with phytohaemagglutinin (PHA) was assessed prospectively in 90 patients with stage I-III breast cancer. Whereas PHA-induced proliferation of PBMCs derived from patients with breast cancer preoperatively was significantly decreased when compared with data obtained in healthy control individuals (P < 0.001), the degree of the defect in PHA-induced proliferation of PBMCs depended upon the tumour burden as manifested by tumour size and axillary lymph node involvement (P < 0.003 in each case). PHA-induced proliferation of PBMCs dropped significantly in patients who received adjuvant chemotherapy consisting of cyclophosphamide, methotrexate and fluorouracil (CMF) after an observation period of 6 months (P < 0.01), but not in patients under adjuvant treatment with tamoxifen only. After an additional 6 months (i.e. 12 months after surgery), PHA-induced proliferation of PBMCs was similar in patients after adjuvant chemotherapy with CMF and in those receiving continued adjuvant tamoxifen treatment (P > 0.1), but in all patients still significantly decreased as compared with healthy controls (P < 0.001). When data obtained preoperatively and after 12 months were compared, it was found that out of 23 patients whose PBMCs had experienced a drop in their PHA-induced proliferation, 14 (61%) had developed metastatic disease within the subsequent 24 months (i.e. 36 months after surgery). In contrast, out of 59 patients whose PBMCs showed an increase in their PHA-induced proliferation within the first 12 months after surgery, only one (2%) presented with disease progression. We thus conclude that PHA-induced proliferation of PBMCs derived from patients with breast cancer depends upon the tumour load and is a good clinical predictor for the further course of the disease." ], "offsets": [ [ 161, 2150 ] ] } ]

[ { "id": "4783", "type": "other_name", "text": [ "mitogenic stimulation" ], "offsets": [ [ 8, 29 ] ], "normalized": [] }, { "id": "4784", "type": "cell_type", "text": [ "peripheral blood mononuclear cells" ], "offsets": [ [ 33, 67 ] ], "normalized": [] }, { "id": "4785", "type": "other_name", "text": [ "breast cancer" ], "offsets": [ [ 112, 125 ] ], "normalized": [] }, { "id": "4786", "type": "other_name", "text": [ "prospective longitudinal study" ], "offsets": [ [ 129, 159 ] ], "normalized": [] }, { "id": "4787", "type": "other_name", "text": [ "Immunosuppression" ], "offsets": [ [ 161, 178 ] ], "normalized": [] }, { "id": "4788", "type": "other_name", "text": [ "malignant diseases" ], "offsets": [ [ 224, 242 ] ], "normalized": [] }, { "id": "4789", "type": "cell_type", "text": [ "peripheral blood mononuclear cells" ], "offsets": [ [ 287, 321 ] ], "normalized": [] }, { "id": "4790", "type": "cell_type", "text": [ "PBMCs" ], "offsets": [ [ 323, 328 ] ], "normalized": [] }, { "id": "4791", "type": "other_name", "text": [ "mitogenic stimulation" ], "offsets": [ [ 345, 366 ] ], "normalized": [] }, { "id": "4792", "type": "protein_molecule", "text": [ "phytohaemagglutinin" ], "offsets": [ [ 372, 391 ] ], "normalized": [] }, { "id": "4793", "type": "protein_molecule", "text": [ "PHA" ], "offsets": [ [ 393, 396 ] ], "normalized": [] }, { "id": "4794", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 431, 439 ] ], "normalized": [] }, { "id": "4795", "type": "other_name", "text": [ "breast cancer" ], "offsets": [ [ 457, 470 ] ], "normalized": [] }, { "id": "4796", "type": "other_name", "text": [ "PHA-induced proliferation" ], "offsets": [ [ 480, 505 ] ], "normalized": [] }, { "id": "4797", "type": "protein_molecule", "text": [ "PHA" ], "offsets": [ [ 480, 483 ] ], "normalized": [] }, { "id": "4798", "type": "cell_type", "text": [ "PBMCs" ], "offsets": [ [ 509, 514 ] ], "normalized": [] }, { "id": "4799", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 528, 536 ] ], "normalized": [] }, { "id": "4800", "type": "other_name", "text": [ "breast cancer" ], "offsets": [ [ 542, 555 ] ], "normalized": [] }, { "id": "4801", "type": "multi_cell", "text": [ "healthy control individuals" ], "offsets": [ [ 635, 662 ] ], "normalized": [] }, { "id": "4802", "type": "other_name", "text": [ "PHA-induced proliferation" ], "offsets": [ [ 704, 729 ] ], "normalized": [] }, { "id": "4803", "type": "protein_molecule", "text": [ "PHA" ], "offsets": [ [ 704, 707 ] ], "normalized": [] }, { "id": "4804", "type": "cell_type", "text": [ "PBMCs" ], "offsets": [ [ 733, 738 ] ], "normalized": [] }, { "id": "4805", "type": "other_name", "text": [ "tumour size" ], "offsets": [ [ 788, 799 ] ], "normalized": [] }, { "id": "4806", "type": "body_part", "text": [ "axillary lymph node" ], "offsets": [ [ 804, 823 ] ], "normalized": [] }, { "id": "4807", "type": "other_name", "text": [ "PHA-induced proliferation" ], "offsets": [ [ 862, 887 ] ], "normalized": [] }, { "id": "4808", "type": "protein_molecule", "text": [ "PHA" ], "offsets": [ [ 862, 865 ] ], "normalized": [] }, { "id": "4809", "type": "cell_type", "text": [ "PBMCs" ], "offsets": [ [ 891, 896 ] ], "normalized": [] }, { "id": "4810", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 922, 930 ] ], "normalized": [] }, { "id": "4811", "type": "other_organic_compound", "text": [ "cyclophosphamide" ], "offsets": [ [ 980, 996 ] ], "normalized": [] }, { "id": "4812", "type": "other_organic_compound", "text": [ "methotrexate" ], "offsets": [ [ 998, 1010 ] ], "normalized": [] }, { "id": "4813", "type": "other_organic_compound", "text": [ "fluorouracil" ], "offsets": [ [ 1015, 1027 ] ], "normalized": [] }, { "id": "4814", "type": "other_organic_compound", "text": [ "CMF" ], "offsets": [ [ 1029, 1032 ] ], "normalized": [] }, { "id": "4815", "type": "other_name", "text": [ "observation period" ], "offsets": [ [ 1043, 1061 ] ], "normalized": [] }, { "id": "4816", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 1097, 1105 ] ], "normalized": [] }, { "id": "4817", "type": "other_organic_compound", "text": [ "tamoxifen" ], "offsets": [ [ 1136, 1145 ] ], "normalized": [] }, { "id": "4818", "type": "other_name", "text": [ "PHA-induced proliferation" ], "offsets": [ [ 1213, 1238 ] ], "normalized": [] }, { "id": "4819", "type": "protein_molecule", "text": [ "PHA" ], "offsets": [ [ 1213, 1216 ] ], "normalized": [] }, { "id": "4820", "type": "cell_type", "text": [ "PBMCs" ], "offsets": [ [ 1242, 1247 ] ], "normalized": [] }, { "id": "4821", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 1263, 1271 ] ], "normalized": [] }, { "id": "4822", "type": "other_name", "text": [ "adjuvant chemotherapy" ], "offsets": [ [ 1278, 1299 ] ], "normalized": [] }, { "id": "4823", "type": "other_organic_compound", "text": [ "CMF" ], "offsets": [ [ 1305, 1308 ] ], "normalized": [] }, { "id": "4824", "type": "other_name", "text": [ "adjuvant tamoxifen treatment" ], "offsets": [ [ 1342, 1370 ] ], "normalized": [] }, { "id": "4825", "type": "other_organic_compound", "text": [ "tamoxifen" ], "offsets": [ [ 1351, 1360 ] ], "normalized": [] }, { "id": "4826", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 1393, 1401 ] ], "normalized": [] }, { "id": "4827", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 1576, 1584 ] ], "normalized": [] }, { "id": "4828", "type": "cell_type", "text": [ "PBMCs" ], "offsets": [ [ 1591, 1596 ] ], "normalized": [] }, { "id": "4829", "type": "other_name", "text": [ "PHA-induced proliferation" ], "offsets": [ [ 1629, 1654 ] ], "normalized": [] }, { "id": "4830", "type": "protein_molecule", "text": [ "PHA" ], "offsets": [ [ 1629, 1632 ] ], "normalized": [] }, { "id": "4831", "type": "other_name", "text": [ "metastatic disease" ], "offsets": [ [ 1679, 1697 ] ], "normalized": [] }, { "id": "4832", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 1785, 1793 ] ], "normalized": [] }, { "id": "4833", "type": "cell_type", "text": [ "PBMCs" ], "offsets": [ [ 1800, 1805 ] ], "normalized": [] }, { "id": "4834", "type": "other_name", "text": [ "PHA-induced proliferation" ], "offsets": [ [ 1834, 1859 ] ], "normalized": [] }, { "id": "4835", "type": "protein_molecule", "text": [ "PHA" ], "offsets": [ [ 1834, 1837 ] ], "normalized": [] }, { "id": "4836", "type": "other_name", "text": [ "disease progression" ], "offsets": [ [ 1931, 1950 ] ], "normalized": [] }, { "id": "4837", "type": "other_name", "text": [ "PHA-induced proliferation" ], "offsets": [ [ 1974, 1999 ] ], "normalized": [] }, { "id": "4838", "type": "protein_molecule", "text": [ "PHA" ], "offsets": [ [ 1974, 1977 ] ], "normalized": [] }, { "id": "4839", "type": "cell_type", "text": [ "PBMCs" ], "offsets": [ [ 2003, 2008 ] ], "normalized": [] }, { "id": "4840", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 2022, 2030 ] ], "normalized": [] }, { "id": "4841", "type": "other_name", "text": [ "breast cancer" ], "offsets": [ [ 2036, 2049 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "4843", "type": "title", "text": [ "Activation of transcription by binding of NF-E1 (YY1) to a newly identified element in the first exon of the human DR alpha gene." ], "offsets": [ [ 0, 129 ] ] }, { "id": "4844", "type": "abstract", "text": [ "A previously unrecognized element, located downstream of the start site of transcription in the first exon of the DR alpha gene, has been defined that enhances promoter activity up to eightfold in a position-dependent manner. Mutations in this DNA-binding site abolished binding of a nuclear factor in human B cell nuclear extract and decreased the activity of the DR alpha promoter to a basal level. Significant sequence homology of this element was found in the DNA of the DR beta, DP alpha and -beta, and DQ alpha genes, always located downstream of the transcriptional start site. The nuclear factor binds to the DR alpha and DP alpha element but not to the element in the DQ alpha gene. It was identified as NF-E1 (YY1). This protein, previously identified by its binding to the Ig kappa 3' enhancer and the Ig heavy chain mu E1 site, thus also appears to be quite important in the regulation of MHC class II gene expression." ], "offsets": [ [ 130, 1060 ] ] } ]

[ { "id": "4845", "type": "other_name", "text": [ "Activation of transcription" ], "offsets": [ [ 0, 27 ] ], "normalized": [] }, { "id": "4846", "type": "protein_molecule", "text": [ "NF-E1" ], "offsets": [ [ 42, 47 ] ], "normalized": [] }, { "id": "4847", "type": "protein_molecule", "text": [ "YY1" ], "offsets": [ [ 49, 52 ] ], "normalized": [] }, { "id": "4848", "type": "DNA_domain_or_region", "text": [ "human DR alpha gene" ], "offsets": [ [ 109, 128 ] ], "normalized": [] }, { "id": "4849", "type": "DNA_domain_or_region", "text": [ "start site of transcription" ], "offsets": [ [ 191, 218 ] ], "normalized": [] }, { "id": "4850", "type": "DNA_domain_or_region", "text": [ "exon" ], "offsets": [ [ 232, 236 ] ], "normalized": [] }, { "id": "4851", "type": "DNA_domain_or_region", "text": [ "DR alpha gene" ], "offsets": [ [ 244, 257 ] ], "normalized": [] }, { "id": "4852", "type": "other_name", "text": [ "promoter activity" ], "offsets": [ [ 290, 307 ] ], "normalized": [] }, { "id": "4853", "type": "other_name", "text": [ "position-dependent manner" ], "offsets": [ [ 329, 354 ] ], "normalized": [] }, { "id": "4854", "type": "DNA_domain_or_region", "text": [ "DNA-binding site" ], "offsets": [ [ 374, 390 ] ], "normalized": [] }, { "id": "4855", "type": "protein_family_or_group", "text": [ "nuclear factor" ], "offsets": [ [ 414, 428 ] ], "normalized": [] }, { "id": "4856", "type": "cell_component", "text": [ "human B cell nuclear extract" ], "offsets": [ [ 432, 460 ] ], "normalized": [] }, { "id": "4857", "type": "DNA_domain_or_region", "text": [ "DR alpha promoter" ], "offsets": [ [ 495, 512 ] ], "normalized": [] }, { "id": "4858", "type": "other_name", "text": [ "basal level" ], "offsets": [ [ 518, 529 ] ], "normalized": [] }, { "id": "4859", "type": "DNA_domain_or_region", "text": [ "element" ], "offsets": [ [ 569, 576 ] ], "normalized": [] }, { "id": "4860", "type": "(AND DNA_domain_or_region DNA_domain_or_region DNA_domain_or_region DNA_domain_or_region)", "text": [ "DR beta, DP alpha and -beta, and DQ alpha genes" ], "offsets": [ [ 605, 652 ] ], "normalized": [] }, { "id": "4861", "type": "", "text": [ "DR beta" ], "offsets": [ [ 605, 612 ] ], "normalized": [] }, { "id": "4862", "type": "(AND DNA_domain_or_region DNA_domain_or_region)", "text": [ "DP alpha and -beta" ], "offsets": [ [ 614, 632 ] ], "normalized": [] }, { "id": "4863", "type": "", "text": [ "DP" ], "offsets": [ [ 614, 616 ] ], "normalized": [] }, { "id": "4864", "type": "", "text": [ "alpha" ], "offsets": [ [ 617, 622 ] ], "normalized": [] }, { "id": "4865", "type": "", "text": [ "-beta" ], "offsets": [ [ 627, 632 ] ], "normalized": [] }, { "id": "4866", "type": "", "text": [ "DQ alpha" ], "offsets": [ [ 638, 646 ] ], "normalized": [] }, { "id": "4867", "type": "", "text": [ "genes" ], "offsets": [ [ 647, 652 ] ], "normalized": [] }, { "id": "4868", "type": "DNA_domain_or_region", "text": [ "transcriptional start site" ], "offsets": [ [ 687, 713 ] ], "normalized": [] }, { "id": "4869", "type": "(AND DNA_domain_or_region DNA_domain_or_region)", "text": [ "DR alpha and DP alpha element" ], "offsets": [ [ 747, 776 ] ], "normalized": [] }, { "id": "4870", "type": "", "text": [ "DR alpha" ], "offsets": [ [ 747, 755 ] ], "normalized": [] }, { "id": "4871", "type": "", "text": [ "DP alpha" ], "offsets": [ [ 760, 768 ] ], "normalized": [] }, { "id": "4872", "type": "", "text": [ "element" ], "offsets": [ [ 769, 776 ] ], "normalized": [] }, { "id": "4873", "type": "DNA_domain_or_region", "text": [ "DQ alpha gene" ], "offsets": [ [ 807, 820 ] ], "normalized": [] }, { "id": "4874", "type": "protein_molecule", "text": [ "NF-E1" ], "offsets": [ [ 843, 848 ] ], "normalized": [] }, { "id": "4875", "type": "protein_molecule", "text": [ "YY1" ], "offsets": [ [ 850, 853 ] ], "normalized": [] }, { "id": "4876", "type": "DNA_domain_or_region", "text": [ "Ig kappa 3' enhancer" ], "offsets": [ [ 914, 934 ] ], "normalized": [] }, { "id": "4877", "type": "DNA_domain_or_region", "text": [ "Ig heavy chain mu E1 site" ], "offsets": [ [ 943, 968 ] ], "normalized": [] }, { "id": "4878", "type": "protein_complex", "text": [ "Ig heavy chain" ], "offsets": [ [ 943, 957 ] ], "normalized": [] }, { "id": "4879", "type": "other_name", "text": [ "MHC class II gene expression" ], "offsets": [ [ 1031, 1059 ] ], "normalized": [] }, { "id": "4880", "type": "DNA_family_or_group", "text": [ "MHC class II gene" ], "offsets": [ [ 1031, 1048 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "4882", "type": "title", "text": [ "Transcriptional activity of core binding factor-alpha (AML1) and beta subunits on murine leukemia virus enhancer cores." ], "offsets": [ [ 0, 119 ] ] }, { "id": "4883", "type": "abstract", "text": [ "Core binding factor (CBF), also known as polyomavirus enhancer-binding protein 2 and SL3 enhancer factor 1, is a mammalian transcription factor that binds to an element termed the core within the enhancers of the murine leukemia virus family of retroviruses. The core elements of the SL3 virus are important genetic determinants of the ability of this virus to induce T-cell lymphomas and the transcriptional activity of the viral long terminal repeat in T lymphocytes. CBF consists of two subunits, a DNA binding subunit, CBF alpha, and a second subunit, CBF beta, that stimulates the DNA binding activity of CBF alpha. One of the genes that encodes a CBF alpha subunit is AML1, also called Cbf alpha 2. This locus is rearranged by chromosomal translocations in human myeloproliferative disorders and leukemias. An exogenously expressed Cbf alpha 2-encoded subunit (CBF alpha 2-451) stimulated transcription from the SL3 enhancer in P19 and HeLa cells. Activity was mediated through the core elements. Three different isoforms of CBF beta were also tested for transcriptional activity on the SL3 enhancer. The longest form, CBF beta-187, increased the transcriptional stimulation by CBF alpha 2-451 twofold in HeLa cells, although it had no effect in P19 cells. Transcriptional activation by CBF beta required binding to the CBF alpha subunit, as a form of CBF beta that lacked binding ability, CBF beta-148, failed to increase activity. These results indicated that at least in certain cell types, the maximum activity of CBF required both subunits. They also provided support for the hypothesis that CBF is a factor in T lymphocytes that is responsible for recognition of the SL3 cores. We also examined whether CBF could distinguish a 1-bp difference between the enhancer core of SL3 and the core of the nonleukemogenic virus, Akv. This difference strongly affects transcription in T cells and leukemogenicity of SL3. However, no combination of CBF alpha and CBF beta subunits that we tested was able to distinguish the 1-bp difference in transcription assays. Thus, a complete understanding of how T cells recognize the SL3 core remains to be elucidated." ], "offsets": [ [ 120, 2279 ] ] } ]

[ { "id": "4884", "type": "other_name", "text": [ "Transcriptional activity" ], "offsets": [ [ 0, 24 ] ], "normalized": [] }, { "id": "4885", "type": "(AND protein_subunit protein_subunit)", "text": [ "core binding factor-alpha (AML1) and beta" ], "offsets": [ [ 28, 69 ] ], "normalized": [] }, { "id": "4886", "type": "", "text": [ "core binding factor-" ], "offsets": [ [ 28, 48 ] ], "normalized": [] }, { "id": "4887", "type": "", "text": [ "alpha (AML1)" ], "offsets": [ [ 48, 60 ] ], "normalized": [] }, { "id": "4888", "type": "", "text": [ "beta" ], "offsets": [ [ 65, 69 ] ], "normalized": [] }, { "id": "4889", "type": "DNA_domain_or_region", "text": [ "murine leukemia virus enhancer cores" ], "offsets": [ [ 82, 118 ] ], "normalized": [] }, { "id": "4890", "type": "virus", "text": [ "murine leukemia virus" ], "offsets": [ [ 82, 103 ] ], "normalized": [] }, { "id": "4891", "type": "protein_family_or_group", "text": [ "Core binding factor" ], "offsets": [ [ 120, 139 ] ], "normalized": [] }, { "id": "4892", "type": "protein_molecule", "text": [ "CBF" ], "offsets": [ [ 141, 144 ] ], "normalized": [] }, { "id": "4893", "type": "protein_family_or_group", "text": [ "polyomavirus enhancer-binding protein 2" ], "offsets": [ [ 161, 200 ] ], "normalized": [] }, { "id": "4894", "type": "protein_molecule", "text": [ "SL3 enhancer factor 1" ], "offsets": [ [ 205, 226 ] ], "normalized": [] }, { "id": "4895", "type": "protein_family_or_group", "text": [ "mammalian transcription factor" ], "offsets": [ [ 233, 263 ] ], "normalized": [] }, { "id": "4896", "type": "DNA_domain_or_region", "text": [ "enhancers" ], "offsets": [ [ 316, 325 ] ], "normalized": [] }, { "id": "4897", "type": "virus", "text": [ "murine leukemia virus family" ], "offsets": [ [ 333, 361 ] ], "normalized": [] }, { "id": "4898", "type": "virus", "text": [ "retroviruses" ], "offsets": [ [ 365, 377 ] ], "normalized": [] }, { "id": "4899", "type": "DNA_domain_or_region", "text": [ "core elements" ], "offsets": [ [ 383, 396 ] ], "normalized": [] }, { "id": "4900", "type": "virus", "text": [ "SL3 virus" ], "offsets": [ [ 404, 413 ] ], "normalized": [] }, { "id": "4901", "type": "other_name", "text": [ "T-cell lymphomas" ], "offsets": [ [ 488, 504 ] ], "normalized": [] }, { "id": "4902", "type": "other_name", "text": [ "transcriptional activity" ], "offsets": [ [ 513, 537 ] ], "normalized": [] }, { "id": "4903", "type": "DNA_domain_or_region", "text": [ "viral long terminal repeat" ], "offsets": [ [ 545, 571 ] ], "normalized": [] }, { "id": "4904", "type": "cell_type", "text": [ "T lymphocytes" ], "offsets": [ [ 575, 588 ] ], "normalized": [] }, { "id": "4905", "type": "protein_molecule", "text": [ "CBF" ], "offsets": [ [ 590, 593 ] ], "normalized": [] }, { "id": "4906", "type": "protein_subunit", "text": [ "DNA binding subunit" ], "offsets": [ [ 622, 641 ] ], "normalized": [] }, { "id": "4907", "type": "protein_subunit", "text": [ "CBF alpha" ], "offsets": [ [ 643, 652 ] ], "normalized": [] }, { "id": "4908", "type": "protein_subunit", "text": [ "CBF beta" ], "offsets": [ [ 676, 684 ] ], "normalized": [] }, { "id": "4909", "type": "other_name", "text": [ "DNA binding activity" ], "offsets": [ [ 706, 726 ] ], "normalized": [] }, { "id": "4910", "type": "protein_subunit", "text": [ "CBF alpha" ], "offsets": [ [ 730, 739 ] ], "normalized": [] }, { "id": "4911", "type": "protein_subunit", "text": [ "CBF alpha subunit" ], "offsets": [ [ 773, 790 ] ], "normalized": [] }, { "id": "4912", "type": "protein_subunit", "text": [ "CBF alpha" ], "offsets": [ [ 773, 782 ] ], "normalized": [] }, { "id": "4913", "type": "protein_subunit", "text": [ "AML1" ], "offsets": [ [ 794, 798 ] ], "normalized": [] }, { "id": "4914", "type": "protein_molecule", "text": [ "Cbf alpha 2" ], "offsets": [ [ 812, 823 ] ], "normalized": [] }, { "id": "4915", "type": "other_name", "text": [ "chromosomal translocations" ], "offsets": [ [ 853, 879 ] ], "normalized": [] }, { "id": "4916", "type": "other_name", "text": [ "human myeloproliferative disorders" ], "offsets": [ [ 883, 917 ] ], "normalized": [] }, { "id": "4917", "type": "other_name", "text": [ "leukemias" ], "offsets": [ [ 922, 931 ] ], "normalized": [] }, { "id": "4918", "type": "protein_subunit", "text": [ "Cbf alpha 2-encoded subunit" ], "offsets": [ [ 958, 985 ] ], "normalized": [] }, { "id": "4919", "type": "protein_molecule", "text": [ "Cbf alpha 2" ], "offsets": [ [ 958, 969 ] ], "normalized": [] }, { "id": "4920", "type": "protein_subunit", "text": [ "CBF alpha 2-451" ], "offsets": [ [ 987, 1002 ] ], "normalized": [] }, { "id": "4921", "type": "protein_subunit", "text": [ "CBF alpha" ], "offsets": [ [ 987, 996 ] ], "normalized": [] }, { "id": "4922", "type": "DNA_domain_or_region", "text": [ "SL3 enhancer" ], "offsets": [ [ 1038, 1050 ] ], "normalized": [] }, { "id": "4923", "type": "protein_molecule", "text": [ "P19" ], "offsets": [ [ 1054, 1057 ] ], "normalized": [] }, { "id": "4924", "type": "cell_line", "text": [ "HeLa cells" ], "offsets": [ [ 1062, 1072 ] ], "normalized": [] }, { "id": "4925", "type": "DNA_domain_or_region", "text": [ "core elements" ], "offsets": [ [ 1108, 1121 ] ], "normalized": [] }, { "id": "4926", "type": "protein_subunit", "text": [ "CBF beta" ], "offsets": [ [ 1151, 1159 ] ], "normalized": [] }, { "id": "4927", "type": "other_name", "text": [ "transcriptional activity" ], "offsets": [ [ 1181, 1205 ] ], "normalized": [] }, { "id": "4928", "type": "DNA_domain_or_region", "text": [ "SL3 enhancer" ], "offsets": [ [ 1213, 1225 ] ], "normalized": [] }, { "id": "4929", "type": "protein_subunit", "text": [ "CBF beta-187" ], "offsets": [ [ 1245, 1257 ] ], "normalized": [] }, { "id": "4930", "type": "protein_subunit", "text": [ "CBF beta" ], "offsets": [ [ 1245, 1253 ] ], "normalized": [] }, { "id": "4931", "type": "other_name", "text": [ "transcriptional stimulation" ], "offsets": [ [ 1273, 1300 ] ], "normalized": [] }, { "id": "4932", "type": "protein_subunit", "text": [ "CBF alpha 2-451" ], "offsets": [ [ 1304, 1319 ] ], "normalized": [] }, { "id": "4933", "type": "protein_subunit", "text": [ "CBF alpha" ], "offsets": [ [ 1304, 1313 ] ], "normalized": [] }, { "id": "4934", "type": "cell_line", "text": [ "HeLa cells" ], "offsets": [ [ 1331, 1341 ] ], "normalized": [] }, { "id": "4935", "type": "cell_line", "text": [ "P19 cells" ], "offsets": [ [ 1372, 1381 ] ], "normalized": [] }, { "id": "4936", "type": "protein_molecule", "text": [ "P19" ], "offsets": [ [ 1372, 1375 ] ], "normalized": [] }, { "id": "4937", "type": "protein_subunit", "text": [ "CBF beta" ], "offsets": [ [ 1413, 1421 ] ], "normalized": [] }, { "id": "4938", "type": "protein_subunit", "text": [ "CBF alpha subunit" ], "offsets": [ [ 1446, 1463 ] ], "normalized": [] }, { "id": "4939", "type": "protein_subunit", "text": [ "CBF alpha" ], "offsets": [ [ 1446, 1455 ] ], "normalized": [] }, { "id": "4940", "type": "protein_subunit", "text": [ "CBF beta" ], "offsets": [ [ 1478, 1486 ] ], "normalized": [] }, { "id": "4941", "type": "other_name", "text": [ "binding ability," ], "offsets": [ [ 1499, 1515 ] ], "normalized": [] }, { "id": "4942", "type": "protein_subunit", "text": [ "CBF beta-148" ], "offsets": [ [ 1516, 1528 ] ], "normalized": [] }, { "id": "4943", "type": "protein_subunit", "text": [ "CBF beta" ], "offsets": [ [ 1516, 1524 ] ], "normalized": [] }, { "id": "4944", "type": "protein_molecule", "text": [ "CBF" ], "offsets": [ [ 1644, 1647 ] ], "normalized": [] }, { "id": "4945", "type": "protein_molecule", "text": [ "CBF" ], "offsets": [ [ 1723, 1726 ] ], "normalized": [] }, { "id": "4946", "type": "cell_type", "text": [ "T lymphocytes" ], "offsets": [ [ 1742, 1755 ] ], "normalized": [] }, { "id": "4947", "type": "DNA_domain_or_region", "text": [ "SL3 cores" ], "offsets": [ [ 1799, 1808 ] ], "normalized": [] }, { "id": "4948", "type": "protein_molecule", "text": [ "CBF" ], "offsets": [ [ 1835, 1838 ] ], "normalized": [] }, { "id": "4949", "type": "other_name", "text": [ "1-bp difference" ], "offsets": [ [ 1859, 1874 ] ], "normalized": [] }, { "id": "4950", "type": "DNA_substructure", "text": [ "enhancer core of SL3" ], "offsets": [ [ 1887, 1907 ] ], "normalized": [] }, { "id": "4951", "type": "virus", "text": [ "nonleukemogenic virus" ], "offsets": [ [ 1928, 1949 ] ], "normalized": [] }, { "id": "4952", "type": "virus", "text": [ "Akv" ], "offsets": [ [ 1951, 1954 ] ], "normalized": [] }, { "id": "4953", "type": "other_name", "text": [ "leukemogenicity" ], "offsets": [ [ 2018, 2033 ] ], "normalized": [] }, { "id": "4954", "type": "DNA_domain_or_region", "text": [ "SL3" ], "offsets": [ [ 2037, 2040 ] ], "normalized": [] }, { "id": "4955", "type": "protein_subunit", "text": [ "CBF alpha" ], "offsets": [ [ 2069, 2078 ] ], "normalized": [] }, { "id": "4956", "type": "protein_subunit", "text": [ "CBF beta" ], "offsets": [ [ 2083, 2091 ] ], "normalized": [] }, { "id": "4957", "type": "other_name", "text": [ "1-bp difference" ], "offsets": [ [ 2144, 2159 ] ], "normalized": [] }, { "id": "4958", "type": "other_name", "text": [ "transcription assays" ], "offsets": [ [ 2163, 2183 ] ], "normalized": [] }, { "id": "4959", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 2223, 2230 ] ], "normalized": [] }, { "id": "4960", "type": "DNA_domain_or_region", "text": [ "SL3 core" ], "offsets": [ [ 2245, 2253 ] ], "normalized": [] } ]

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[]

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[ { "id": "4962", "type": "title", "text": [ "Interleukin (IL)-10 inhibits nuclear factor kappa B (NF kappa B) activation in human monocytes. IL-10 and IL-4 suppress cytokine synthesis by different mechanisms." ], "offsets": [ [ 0, 163 ] ] }, { "id": "4963", "type": "abstract", "text": [ "Our previous studies in human monocytes have demonstrated that interleukin (IL)-10 inhibits lipopolysaccharide (LPS)-stimulated production of inflammatory cytokines, IL-1 beta, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha by blocking gene transcription. Using electrophoretic mobility shift assays (EMSA), we now show that, in monocytes stimulated with LPS or TNF alpha, IL-10 inhibits nuclear stimulation of nuclear factor kappa B (NF kappa B), a transcription factor involved in the expression of inflammatory cytokine genes. Several other transcription factors including NF-IL-6, AP-1, AP-2, GR, CREB, Oct-1, and Sp-1 are not affected by IL-10. This selective inhibition by IL-10 of NF kappa B activation occurs rapidly and in a dose-dependent manner and correlates well with IL-10's cytokine synthesis inhibitory activity in terms of both kinetics and dose responsiveness. Furthermore, compounds such as tosylphenylalanyl chloromethyl ketone and pyrrolidinedithiocarbamate that are known to selectively inhibit NF kappa B activation block cytokine gene transcription in LPS-stimulated monocytes. Taken together, these results suggest that inhibition of NF kappa B activation may be an important mechanism for IL-10 suppression of cytokine gene transcription in human monocytes. IL-4, another cytokine that inhibits cytokine mRNA accumulation in monocytes, shows little inhibitory effect on LPS-induced NF kappa B activation. Further examination reveals that, unlike IL-10, IL-4 enhances mRNA degradation and does not suppress cytokine gene transcription. These data indicate that IL-10 and IL-4 inhibit cytokine production by different mechanisms." ], "offsets": [ [ 164, 1820 ] ] } ]

[ { "id": "4964", "type": "protein_molecule", "text": [ "Interleukin (IL)-10" ], "offsets": [ [ 0, 19 ] ], "normalized": [] }, { "id": "4965", "type": "other_name", "text": [ "nuclear factor kappa B (NF kappa B) activation" ], "offsets": [ [ 29, 75 ] ], "normalized": [] }, { "id": "4966", "type": "protein_molecule", "text": [ "nuclear factor kappa B" ], "offsets": [ [ 29, 51 ] ], "normalized": [] }, { "id": "4967", "type": "protein_molecule", "text": [ "NF kappa B" ], "offsets": [ [ 53, 63 ] ], "normalized": [] }, { "id": "4968", "type": "cell_type", "text": [ "human monocytes" ], "offsets": [ [ 79, 94 ] ], "normalized": [] }, { "id": "4969", "type": "protein_molecule", "text": [ "IL-10" ], "offsets": [ [ 96, 101 ] ], "normalized": [] }, { "id": "4970", "type": "protein_molecule", "text": [ "IL-4" ], "offsets": [ [ 106, 110 ] ], "normalized": [] }, { "id": "4971", "type": "other_name", "text": [ "cytokine synthesis" ], "offsets": [ [ 120, 138 ] ], "normalized": [] }, { "id": "4972", "type": "protein_family_or_group", "text": [ "cytokine" ], "offsets": [ [ 120, 128 ] ], "normalized": [] }, { "id": "4973", "type": "cell_type", "text": [ "human monocytes" ], "offsets": [ [ 188, 203 ] ], "normalized": [] }, { "id": "4974", "type": "protein_molecule", "text": [ "interleukin (IL)-10" ], "offsets": [ [ 227, 246 ] ], "normalized": [] }, { "id": "4975", "type": "other_name", "text": [ "lipopolysaccharide (LPS)-stimulated production" ], "offsets": [ [ 256, 302 ] ], "normalized": [] }, { "id": "4976", "type": "lipid", "text": [ "lipopolysaccharide" ], "offsets": [ [ 256, 274 ] ], "normalized": [] }, { "id": "4977", "type": "protein_family_or_group", "text": [ "inflammatory cytokines" ], "offsets": [ [ 306, 328 ] ], "normalized": [] }, { "id": "4978", "type": "protein_molecule", "text": [ "IL-1 beta" ], "offsets": [ [ 330, 339 ] ], "normalized": [] }, { "id": "4979", "type": "protein_molecule", "text": [ "IL-6" ], "offsets": [ [ 341, 345 ] ], "normalized": [] }, { "id": "4980", "type": "protein_molecule", "text": [ "IL-8" ], "offsets": [ [ 347, 351 ] ], "normalized": [] }, { "id": "4981", "type": "protein_molecule", "text": [ "tumor necrosis factor (TNF)-alpha" ], "offsets": [ [ 357, 390 ] ], "normalized": [] }, { "id": "4982", "type": "other_name", "text": [ "gene transcription" ], "offsets": [ [ 403, 421 ] ], "normalized": [] }, { "id": "4983", "type": "other_name", "text": [ "electrophoretic mobility shift assays" ], "offsets": [ [ 429, 466 ] ], "normalized": [] }, { "id": "4984", "type": "other_name", "text": [ "EMSA" ], "offsets": [ [ 468, 472 ] ], "normalized": [] }, { "id": "4985", "type": "lipid", "text": [ "LPS" ], "offsets": [ [ 522, 525 ] ], "normalized": [] }, { "id": "4986", "type": "protein_molecule", "text": [ "TNF alpha" ], "offsets": [ [ 529, 538 ] ], "normalized": [] }, { "id": "4987", "type": "protein_molecule", "text": [ "IL-10" ], "offsets": [ [ 540, 545 ] ], "normalized": [] }, { "id": "4988", "type": "protein_molecule", "text": [ "nuclear factor kappa B" ], "offsets": [ [ 578, 600 ] ], "normalized": [] }, { "id": "4989", "type": "protein_molecule", "text": [ "NF kappa B" ], "offsets": [ [ 602, 612 ] ], "normalized": [] }, { "id": "4990", "type": "protein_family_or_group", "text": [ "transcription factor" ], "offsets": [ [ 617, 637 ] ], "normalized": [] }, { "id": "4991", "type": "DNA_family_or_group", "text": [ "inflammatory cytokine genes" ], "offsets": [ [ 668, 695 ] ], "normalized": [] }, { "id": "4992", "type": "protein_family_or_group", "text": [ "transcription factors" ], "offsets": [ [ 711, 732 ] ], "normalized": [] }, { "id": "4993", "type": "protein_molecule", "text": [ "IL-6" ], "offsets": [ [ 746, 750 ] ], "normalized": [] }, { "id": "4994", "type": "protein_molecule", "text": [ "AP-1" ], "offsets": [ [ 752, 756 ] ], "normalized": [] }, { "id": "4995", "type": "protein_molecule", "text": [ "AP-2" ], "offsets": [ [ 758, 762 ] ], "normalized": [] }, { "id": "4996", "type": "protein_family_or_group", "text": [ "GR" ], "offsets": [ [ 764, 766 ] ], "normalized": [] }, { "id": "4997", "type": "protein_family_or_group", "text": [ "CREB" ], "offsets": [ [ 768, 772 ] ], "normalized": [] }, { "id": "4998", "type": "protein_molecule", "text": [ "Oct-1" ], "offsets": [ [ 774, 779 ] ], "normalized": [] }, { "id": "4999", "type": "protein_molecule", "text": [ "Sp-1" ], "offsets": [ [ 785, 789 ] ], "normalized": [] }, { "id": "5000", "type": "protein_molecule", "text": [ "IL-10" ], "offsets": [ [ 810, 815 ] ], "normalized": [] }, { "id": "5001", "type": "protein_molecule", "text": [ "IL-10" ], "offsets": [ [ 846, 851 ] ], "normalized": [] }, { "id": "5002", "type": "other_name", "text": [ "NF kappa B activation" ], "offsets": [ [ 855, 876 ] ], "normalized": [] }, { "id": "5003", "type": "protein_molecule", "text": [ "NF kappa B" ], "offsets": [ [ 855, 865 ] ], "normalized": [] }, { "id": "5004", "type": "other_name", "text": [ "IL-10's cytokine synthesis inhibitory activity" ], "offsets": [ [ 948, 994 ] ], "normalized": [] }, { "id": "5005", "type": "protein_molecule", "text": [ "IL-10" ], "offsets": [ [ 948, 953 ] ], "normalized": [] }, { "id": "5006", "type": "protein_family_or_group", "text": [ "cytokine" ], "offsets": [ [ 956, 964 ] ], "normalized": [] }, { "id": "5007", "type": "other_name", "text": [ "kinetics" ], "offsets": [ [ 1012, 1020 ] ], "normalized": [] }, { "id": "5008", "type": "other_name", "text": [ "dose responsiveness" ], "offsets": [ [ 1025, 1044 ] ], "normalized": [] }, { "id": "5009", "type": "other_organic_compound", "text": [ "tosylphenylalanyl chloromethyl ketone" ], "offsets": [ [ 1077, 1114 ] ], "normalized": [] }, { "id": "5010", "type": "other_organic_compound", "text": [ "pyrrolidinedithiocarbamate" ], "offsets": [ [ 1119, 1145 ] ], "normalized": [] }, { "id": "5011", "type": "other_name", "text": [ "NF kappa B activation" ], "offsets": [ [ 1184, 1205 ] ], "normalized": [] }, { "id": "5012", "type": "protein_molecule", "text": [ "NF kappa B" ], "offsets": [ [ 1184, 1194 ] ], "normalized": [] }, { "id": "5013", "type": "other_name", "text": [ "cytokine gene transcription" ], "offsets": [ [ 1212, 1239 ] ], "normalized": [] }, { "id": "5014", "type": "other_name", "text": [ "gene transcription" ], "offsets": [ [ 1221, 1239 ] ], "normalized": [] }, { "id": "5015", "type": "cell_line", "text": [ "LPS-stimulated monocytes" ], "offsets": [ [ 1243, 1267 ] ], "normalized": [] }, { "id": "5016", "type": "lipid", "text": [ "LPS" ], "offsets": [ [ 1243, 1246 ] ], "normalized": [] }, { "id": "5017", "type": "protein_molecule", "text": [ "NF kappa B" ], "offsets": [ [ 1326, 1336 ] ], "normalized": [] }, { "id": "5018", "type": "protein_molecule", "text": [ "IL-10" ], "offsets": [ [ 1382, 1387 ] ], "normalized": [] }, { "id": "5019", "type": "other_name", "text": [ "cytokine gene transcription" ], "offsets": [ [ 1403, 1430 ] ], "normalized": [] }, { "id": "5020", "type": "other_name", "text": [ "gene transcription" ], "offsets": [ [ 1412, 1430 ] ], "normalized": [] }, { "id": "5021", "type": "cell_type", "text": [ "human monocytes" ], "offsets": [ [ 1434, 1449 ] ], "normalized": [] }, { "id": "5022", "type": "protein_molecule", "text": [ "IL-4" ], "offsets": [ [ 1451, 1455 ] ], "normalized": [] }, { "id": "5023", "type": "protein_family_or_group", "text": [ "cytokine" ], "offsets": [ [ 1465, 1473 ] ], "normalized": [] }, { "id": "5024", "type": "other_name", "text": [ "cytokine mRNA accumulation" ], "offsets": [ [ 1488, 1514 ] ], "normalized": [] }, { "id": "5025", "type": "RNA_family_or_group", "text": [ "cytokine mRNA" ], "offsets": [ [ 1488, 1501 ] ], "normalized": [] }, { "id": "5026", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 1518, 1527 ] ], "normalized": [] }, { "id": "5027", "type": "other_name", "text": [ "LPS-induced NF kappa B activation" ], "offsets": [ [ 1563, 1596 ] ], "normalized": [] }, { "id": "5028", "type": "lipid", "text": [ "LPS" ], "offsets": [ [ 1563, 1566 ] ], "normalized": [] }, { "id": "5029", "type": "protein_molecule", "text": [ "NF kappa B" ], "offsets": [ [ 1575, 1585 ] ], "normalized": [] }, { "id": "5030", "type": "protein_molecule", "text": [ "IL-10" ], "offsets": [ [ 1639, 1644 ] ], "normalized": [] }, { "id": "5031", "type": "protein_molecule", "text": [ "IL-4" ], "offsets": [ [ 1646, 1650 ] ], "normalized": [] }, { "id": "5032", "type": "other_name", "text": [ "mRNA degradation" ], "offsets": [ [ 1660, 1676 ] ], "normalized": [] }, { "id": "5033", "type": "RNA_family_or_group", "text": [ "mRNA" ], "offsets": [ [ 1660, 1664 ] ], "normalized": [] }, { "id": "5034", "type": "other_name", "text": [ "gene transcription" ], "offsets": [ [ 1708, 1726 ] ], "normalized": [] }, { "id": "5035", "type": "protein_molecule", "text": [ "IL-10" ], "offsets": [ [ 1753, 1758 ] ], "normalized": [] }, { "id": "5036", "type": "protein_molecule", "text": [ "IL-4" ], "offsets": [ [ 1763, 1767 ] ], "normalized": [] }, { "id": "5037", "type": "other_name", "text": [ "cytokine production" ], "offsets": [ [ 1776, 1795 ] ], "normalized": [] }, { "id": "5038", "type": "protein_family_or_group", "text": [ "cytokine" ], "offsets": [ [ 1776, 1784 ] ], "normalized": [] } ]

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[ { "id": "5040", "type": "title", "text": [ "LMP-1 activates NF-kappa B by targeting the inhibitory molecule I kappa B alpha." ], "offsets": [ [ 0, 80 ] ] }, { "id": "5041", "type": "abstract", "text": [ "LMP-1, an Epstein-Barr virus membrane protein expressed during latent infection, has oncogenic properties, as judged from its ability to transform B lymphocytes and rodent fibroblasts. LMP-1 induces the expression of bcl2, an oncogene which protects cells from apoptosis, as well as of genes encoding other proteins involved in cell regulation and growth control. The mechanisms by which LMP-1 upregulates these proteins is unknown, but it is plausible that LMP-1 modifies signal transduction pathways that result in the activation of one or more transcription factors that ultimately regulate transcription of oncogenic genes. NF-kappa B, a transcription factor controlling the expression of genes involved in cell activation and growth control, has been shown to be activated by LMP-1. The mechanism(s) regulating this activation remains unknown. Our data indicate that increased NF-kappa B DNA binding and functional activity are present in B-lymphoid cells stably or transiently expressing LMP-1. I kappa B alpha is selectively modified in LMP-1-expressing B cells. A phosphorylated form of I kappa B alpha and increased protein turnover-degradation correlate with increased NF-kappa B nuclear translocation. This results in increased transcription of NF-kappa B-dependent-genes, including those encoding p105 and I kappa B alpha (MAD3). These results indicate that LMP-1 activates NF-kappa B in B-cell lines by targeting I kappa B alpha. Identification of the pathways activated by LMP-1 to result in posttranslational modifications of I kappa B alpha will aid in determining the role of this virus-host cell protein interaction in Epstein-Barr virus-mediated oncogenesis." ], "offsets": [ [ 81, 1758 ] ] } ]

[ { "id": "5042", "type": "protein_molecule", "text": [ "LMP-1" ], "offsets": [ [ 0, 5 ] ], "normalized": [] }, { "id": "5043", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 16, 26 ] ], "normalized": [] }, { "id": "5044", "type": "protein_molecule", "text": [ "inhibitory molecule I kappa B alpha" ], "offsets": [ [ 44, 79 ] ], "normalized": [] }, { "id": "5045", "type": "protein_molecule", "text": [ "I kappa B alpha" ], "offsets": [ [ 64, 79 ] ], "normalized": [] }, { "id": "5046", "type": "protein_molecule", "text": [ "LMP-1" ], "offsets": [ [ 81, 86 ] ], "normalized": [] }, { "id": "5047", "type": "protein_family_or_group", "text": [ "Epstein-Barr virus membrane protein" ], "offsets": [ [ 91, 126 ] ], "normalized": [] }, { "id": "5048", "type": "virus", "text": [ "Epstein-Barr virus" ], "offsets": [ [ 91, 109 ] ], "normalized": [] }, { "id": "5049", "type": "other_name", "text": [ "latent infection" ], "offsets": [ [ 144, 160 ] ], "normalized": [] }, { "id": "5050", "type": "other_name", "text": [ "oncogenic properties" ], "offsets": [ [ 166, 186 ] ], "normalized": [] }, { "id": "5051", "type": "cell_type", "text": [ "lymphocytes" ], "offsets": [ [ 230, 241 ] ], "normalized": [] }, { "id": "5052", "type": "cell_type", "text": [ "rodent fibroblasts" ], "offsets": [ [ 246, 264 ] ], "normalized": [] }, { "id": "5053", "type": "protein_molecule", "text": [ "LMP-1" ], "offsets": [ [ 266, 271 ] ], "normalized": [] }, { "id": "5054", "type": "DNA_domain_or_region", "text": [ "bcl2" ], "offsets": [ [ 298, 302 ] ], "normalized": [] }, { "id": "5055", "type": "DNA_family_or_group", "text": [ "oncogene" ], "offsets": [ [ 307, 315 ] ], "normalized": [] }, { "id": "5056", "type": "other_name", "text": [ "apoptosis" ], "offsets": [ [ 342, 351 ] ], "normalized": [] }, { "id": "5057", "type": "other_name", "text": [ "cell regulation" ], "offsets": [ [ 409, 424 ] ], "normalized": [] }, { "id": "5058", "type": "other_name", "text": [ "growth control" ], "offsets": [ [ 429, 443 ] ], "normalized": [] }, { "id": "5059", "type": "protein_molecule", "text": [ "LMP-1" ], "offsets": [ [ 469, 474 ] ], "normalized": [] }, { "id": "5060", "type": "protein_molecule", "text": [ "LMP-1" ], "offsets": [ [ 539, 544 ] ], "normalized": [] }, { "id": "5061", "type": "other_name", "text": [ "signal transduction pathways" ], "offsets": [ [ 554, 582 ] ], "normalized": [] }, { "id": "5062", "type": "protein_family_or_group", "text": [ "transcription factors" ], "offsets": [ [ 628, 649 ] ], "normalized": [] }, { "id": "5063", "type": "DNA_family_or_group", "text": [ "oncogenic genes" ], "offsets": [ [ 692, 707 ] ], "normalized": [] }, { "id": "5064", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 709, 719 ] ], "normalized": [] }, { "id": "5065", "type": "protein_family_or_group", "text": [ "transcription factor" ], "offsets": [ [ 723, 743 ] ], "normalized": [] }, { "id": "5066", "type": "DNA_family_or_group", "text": [ "genes" ], "offsets": [ [ 774, 779 ] ], "normalized": [] }, { "id": "5067", "type": "other_name", "text": [ "growth control" ], "offsets": [ [ 812, 826 ] ], "normalized": [] }, { "id": "5068", "type": "protein_molecule", "text": [ "LMP-1" ], "offsets": [ [ 862, 867 ] ], "normalized": [] }, { "id": "5069", "type": "other_name", "text": [ "NF-kappa B DNA binding" ], "offsets": [ [ 963, 985 ] ], "normalized": [] }, { "id": "5070", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 963, 973 ] ], "normalized": [] }, { "id": "5071", "type": "cell_type", "text": [ "B-lymphoid cells" ], "offsets": [ [ 1025, 1041 ] ], "normalized": [] }, { "id": "5072", "type": "protein_molecule", "text": [ "LMP-1" ], "offsets": [ [ 1075, 1080 ] ], "normalized": [] }, { "id": "5073", "type": "protein_molecule", "text": [ "I kappa B alpha" ], "offsets": [ [ 1082, 1097 ] ], "normalized": [] }, { "id": "5074", "type": "cell_line", "text": [ "LMP-1-expressing B cells" ], "offsets": [ [ 1125, 1149 ] ], "normalized": [] }, { "id": "5075", "type": "protein_molecule", "text": [ "LMP-1" ], "offsets": [ [ 1125, 1130 ] ], "normalized": [] }, { "id": "5076", "type": "cell_type", "text": [ "B cells" ], "offsets": [ [ 1142, 1149 ] ], "normalized": [] }, { "id": "5077", "type": "protein_molecule", "text": [ "I kappa B alpha" ], "offsets": [ [ 1176, 1191 ] ], "normalized": [] }, { "id": "5078", "type": "other_name", "text": [ "protein turnover-degradation" ], "offsets": [ [ 1206, 1234 ] ], "normalized": [] }, { "id": "5079", "type": "other_name", "text": [ "NF-kappa B nuclear translocation" ], "offsets": [ [ 1260, 1292 ] ], "normalized": [] }, { "id": "5080", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 1260, 1270 ] ], "normalized": [] }, { "id": "5081", "type": "DNA_family_or_group", "text": [ "NF-kappa B-dependent-genes" ], "offsets": [ [ 1337, 1363 ] ], "normalized": [] }, { "id": "5082", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 1337, 1347 ] ], "normalized": [] }, { "id": "5083", "type": "protein_molecule", "text": [ "p105" ], "offsets": [ [ 1390, 1394 ] ], "normalized": [] }, { "id": "5084", "type": "protein_molecule", "text": [ "I kappa B alpha" ], "offsets": [ [ 1399, 1414 ] ], "normalized": [] }, { "id": "5085", "type": "DNA_domain_or_region", "text": [ "MAD3" ], "offsets": [ [ 1416, 1420 ] ], "normalized": [] }, { "id": "5086", "type": "protein_molecule", "text": [ "LMP-1" ], "offsets": [ [ 1451, 1456 ] ], "normalized": [] }, { "id": "5087", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 1467, 1477 ] ], "normalized": [] }, { "id": "5088", "type": "cell_line", "text": [ "B-cell lines" ], "offsets": [ [ 1481, 1493 ] ], "normalized": [] }, { "id": "5089", "type": "protein_molecule", "text": [ "I kappa B alpha" ], "offsets": [ [ 1507, 1522 ] ], "normalized": [] }, { "id": "5090", "type": "protein_molecule", "text": [ "LMP-1" ], "offsets": [ [ 1568, 1573 ] ], "normalized": [] }, { "id": "5091", "type": "other_name", "text": [ "posttranslational modifications" ], "offsets": [ [ 1587, 1618 ] ], "normalized": [] }, { "id": "5092", "type": "protein_molecule", "text": [ "I kappa B alpha" ], "offsets": [ [ 1622, 1637 ] ], "normalized": [] }, { "id": "5093", "type": "other_name", "text": [ "virus-host cell protein interaction" ], "offsets": [ [ 1679, 1714 ] ], "normalized": [] }, { "id": "5094", "type": "other_name", "text": [ "Epstein-Barr virus-mediated oncogenesis" ], "offsets": [ [ 1718, 1757 ] ], "normalized": [] }, { "id": "5095", "type": "virus", "text": [ "Epstein-Barr virus" ], "offsets": [ [ 1718, 1736 ] ], "normalized": [] } ]

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[ { "id": "5097", "type": "title", "text": [ "Identification of human TR2 orphan receptor response element in the transcriptional initiation site of the simian virus 40 major late promoter [published erratum appears in J Biol Chem 1995 Nov 3;270(44):26721]" ], "offsets": [ [ 0, 210 ] ] }, { "id": "5098", "type": "abstract", "text": [ "A DNA response element (TR2RE-SV40) for the TR2 orphan receptor, a member of the steroid-thyroid hormone receptor superfamily, has been identified in the simian virus 40 (SV40) +55 region (nucleotide numbers 368-389, 5'-GTTAAGGTTCGTAGGTCATGGA-3'). Electrophoretic mobility shift assay, using in vitro translated TR2 orphan receptor with a molecular mass of 67 kilodaltons, showed a specific binding with high affinity (dissociation constant = 9 nM) for this DNA sequence. DNA-swap experiments using chloramphenicol acetyl-transferase assay demonstrated that androgen can suppress the transcriptional activities of SV40 early promoter via the interaction between this TR2RE-SV40 and the chimeric receptor AR/TR2/AR with the DNA-binding domain of the TR2 orphan receptor flanked by the N-terminal and androgen-binding domains of the androgen receptor. In addition, this TR2RE-SV40 can function as a repressor to suppress the transcriptional activities of both SV40 early and late promoters. Together, these data suggest the TR2RE-SV40 may represent the first identified natural DNA response element for the TR2 orphan receptor that may function as a repressor for the SV40 gene expression." ], "offsets": [ [ 211, 1398 ] ] } ]

[ { "id": "5099", "type": "DNA_domain_or_region", "text": [ "human TR2 orphan receptor response element" ], "offsets": [ [ 18, 60 ] ], "normalized": [] }, { "id": "5100", "type": "protein_molecule", "text": [ "human TR2 orphan receptor" ], "offsets": [ [ 18, 43 ] ], "normalized": [] }, { "id": "5101", "type": "DNA_domain_or_region", "text": [ "transcriptional initiation site" ], "offsets": [ [ 68, 99 ] ], "normalized": [] }, { "id": "5102", "type": "DNA_domain_or_region", "text": [ "simian virus 40 major late promoter" ], "offsets": [ [ 107, 142 ] ], "normalized": [] }, { "id": "5103", "type": "virus", "text": [ "simian virus 40" ], "offsets": [ [ 107, 122 ] ], "normalized": [] }, { "id": "5104", "type": "DNA_domain_or_region", "text": [ "DNA response element" ], "offsets": [ [ 213, 233 ] ], "normalized": [] }, { "id": "5105", "type": "DNA_domain_or_region", "text": [ "TR2RE-SV40" ], "offsets": [ [ 235, 245 ] ], "normalized": [] }, { "id": "5106", "type": "protein_molecule", "text": [ "TR2 orphan receptor" ], "offsets": [ [ 255, 274 ] ], "normalized": [] }, { "id": "5107", "type": "protein_family_or_group", "text": [ "steroid-thyroid hormone receptor superfamily" ], "offsets": [ [ 292, 336 ] ], "normalized": [] }, { "id": "5108", "type": "DNA_domain_or_region", "text": [ "simian virus 40 (SV40) +55 region" ], "offsets": [ [ 365, 398 ] ], "normalized": [] }, { "id": "5109", "type": "virus", "text": [ "simian virus 40" ], "offsets": [ [ 365, 380 ] ], "normalized": [] }, { "id": "5110", "type": "virus", "text": [ "SV40" ], "offsets": [ [ 241, 245 ] ], "normalized": [] }, { "id": "5111", "type": "DNA_domain_or_region", "text": [ "nucleotide numbers 368-389" ], "offsets": [ [ 400, 426 ] ], "normalized": [] }, { "id": "5112", "type": "polynucleotide", "text": [ "5'-GTTAAGGTTCGTAGGTCATGGA-3'" ], "offsets": [ [ 428, 456 ] ], "normalized": [] }, { "id": "5113", "type": "other_name", "text": [ "Electrophoretic mobility shift assay" ], "offsets": [ [ 459, 495 ] ], "normalized": [] }, { "id": "5114", "type": "protein_molecule", "text": [ "TR2 orphan receptor" ], "offsets": [ [ 523, 542 ] ], "normalized": [] }, { "id": "5115", "type": "protein_molecule", "text": [ "67 kilodaltons" ], "offsets": [ [ 568, 582 ] ], "normalized": [] }, { "id": "5116", "type": "DNA_N/A", "text": [ "DNA sequence" ], "offsets": [ [ 669, 681 ] ], "normalized": [] }, { "id": "5117", "type": "other_name", "text": [ "DNA-swap experiments" ], "offsets": [ [ 683, 703 ] ], "normalized": [] }, { "id": "5118", "type": "other_name", "text": [ "chloramphenicol acetyl-transferase assay" ], "offsets": [ [ 710, 750 ] ], "normalized": [] }, { "id": "5119", "type": "protein_molecule", "text": [ "chloramphenicol acetyl-transferase" ], "offsets": [ [ 710, 744 ] ], "normalized": [] }, { "id": "5120", "type": "lipid", "text": [ "androgen" ], "offsets": [ [ 769, 777 ] ], "normalized": [] }, { "id": "5121", "type": "other_name", "text": [ "transcriptional activities" ], "offsets": [ [ 795, 821 ] ], "normalized": [] }, { "id": "5122", "type": "DNA_domain_or_region", "text": [ "SV40 early promoter" ], "offsets": [ [ 825, 844 ] ], "normalized": [] }, { "id": "5123", "type": "virus", "text": [ "SV40" ], "offsets": [ [ 825, 829 ] ], "normalized": [] }, { "id": "5124", "type": "DNA_domain_or_region", "text": [ "TR2RE-SV40" ], "offsets": [ [ 878, 888 ] ], "normalized": [] }, { "id": "5125", "type": "protein_domain_or_region", "text": [ "TR2RE-SV40" ], "offsets": [ [ 878, 888 ] ], "normalized": [] }, { "id": "5126", "type": "virus", "text": [ "SV40" ], "offsets": [ [ 884, 888 ] ], "normalized": [] }, { "id": "5127", "type": "protein_molecule", "text": [ "chimeric receptor AR/TR2/AR" ], "offsets": [ [ 897, 924 ] ], "normalized": [] }, { "id": "5128", "type": "protein_domain_or_region", "text": [ "DNA-binding domain" ], "offsets": [ [ 934, 952 ] ], "normalized": [] }, { "id": "5129", "type": "protein_molecule", "text": [ "TR2 orphan receptor" ], "offsets": [ [ 960, 979 ] ], "normalized": [] }, { "id": "5130", "type": "(AND protein_domain_or_region protein_domain_or_region)", "text": [ "N-terminal and androgen-binding domains" ], "offsets": [ [ 995, 1034 ] ], "normalized": [] }, { "id": "5131", "type": "", "text": [ "N-terminal" ], "offsets": [ [ 995, 1005 ] ], "normalized": [] }, { "id": "5132", "type": "", "text": [ "androgen-binding" ], "offsets": [ [ 1010, 1026 ] ], "normalized": [] }, { "id": "5133", "type": "", "text": [ "domains" ], "offsets": [ [ 1027, 1034 ] ], "normalized": [] }, { "id": "5134", "type": "protein_molecule", "text": [ "androgen receptor" ], "offsets": [ [ 1042, 1059 ] ], "normalized": [] }, { "id": "5135", "type": "DNA_domain_or_region", "text": [ "TR2RE-SV40" ], "offsets": [ [ 1079, 1089 ] ], "normalized": [] }, { "id": "5136", "type": "virus", "text": [ "SV40" ], "offsets": [ [ 1085, 1089 ] ], "normalized": [] }, { "id": "5137", "type": "other_name", "text": [ "transcriptional activities" ], "offsets": [ [ 1134, 1160 ] ], "normalized": [] }, { "id": "5138", "type": "(AND DNA_domain_or_region DNA_domain_or_region)", "text": [ "SV40 early and late promoters" ], "offsets": [ [ 1169, 1198 ] ], "normalized": [] }, { "id": "5139", "type": "", "text": [ "SV40" ], "offsets": [ [ 1085, 1089 ] ], "normalized": [] }, { "id": "5140", "type": "", "text": [ "early" ], "offsets": [ [ 1174, 1179 ] ], "normalized": [] }, { "id": "5141", "type": "", "text": [ "late" ], "offsets": [ [ 1184, 1188 ] ], "normalized": [] }, { "id": "5142", "type": "", "text": [ "promoters" ], "offsets": [ [ 1189, 1198 ] ], "normalized": [] }, { "id": "5143", "type": "DNA_domain_or_region", "text": [ "TR2RE-SV40" ], "offsets": [ [ 1233, 1243 ] ], "normalized": [] }, { "id": "5144", "type": "virus", "text": [ "SV40" ], "offsets": [ [ 1239, 1243 ] ], "normalized": [] }, { "id": "5145", "type": "DNA_domain_or_region", "text": [ "DNA response element" ], "offsets": [ [ 1287, 1307 ] ], "normalized": [] }, { "id": "5146", "type": "protein_molecule", "text": [ "TR2 orphan receptor" ], "offsets": [ [ 1316, 1335 ] ], "normalized": [] }, { "id": "5147", "type": "other_name", "text": [ "SV40 gene expression" ], "offsets": [ [ 1377, 1397 ] ], "normalized": [] }, { "id": "5148", "type": "virus", "text": [ "SV40" ], "offsets": [ [ 1377, 1381 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "5150", "type": "title", "text": [ "Detection of the chromosome 16 CBF beta-MYH11 fusion transcript in myelomonocytic leukemias." ], "offsets": [ [ 0, 92 ] ] }, { "id": "5151", "type": "abstract", "text": [ "Karyotypic detection of chromosomal 16 abnormalities classically associated with AML M4Eo can be difficult. Characterization of the two genes involved in the inv(16)(p13q22), CBF beta and MYH11, has allowed the detection of fusion transcripts by reverse-transcriptase polymerase chain reaction (RT-PCR). We have analyzed CBF beta-MYH11 fusion transcripts by RT-PCR in myelomonocytic leukemias, with or without eosinophilia, to determine whether their presence correlates with morphology. Fifty-three cases (11 AML M4Eo; 1 AML M4 with atypical abnormal eosinophils (AML M4 \"Eo\"); 29 AML M4; 8 AML M5; 3 CMML; and 1 AML M2 with eosinophilia) were analyzed. All 11 typical AML M4Eo were CBF beta-MYH11 positive. The single case of AML M4 with distinctive eosinophil abnormalities was negative by karyotype, RT-PCR and fluorescent in situ hybridization (FISH). Three of 29 (10%) AML M4 without abnormal eosinophils were CBF beta-MYH11 positive, 1 of which did not show any apparent chromosome 16 abnormalities by classical metaphase analysis (2 not tested). Both cases tested also showed MYH11 genomic rearrangement. None of the other leukemias were RT-PCR positive. Follow-up of three patient showed residual positivity in apparent complete remission. These data show that CBF beta-MYH11 fusion transcripts occur not only in the vast majority of typical AML M4Eo, but also in approximately 10% of AML M4 without eosinophilic abnormalities, a much higher incidence than the sporadic reports of chromosome 16 abnormalities in AML M4 would suggest. Taken together with the detection of CBF beta-MYH11 transcripts in the absence of apparent chromosome 16 abnormalities by classical banding techniques, these data show that additional screening by either RT-PCR or FISH should be performed in all AML M4, regardless of morphologic features, to allow accurate evaluation of the prognostic importance of this fusion transcript." ], "offsets": [ [ 93, 2010 ] ] } ]

[ { "id": "5152", "type": "RNA_molecule", "text": [ "chromosome 16 CBF beta-MYH11 fusion transcript" ], "offsets": [ [ 17, 63 ] ], "normalized": [] }, { "id": "5153", "type": "DNA_molecule", "text": [ "chromosome 16" ], "offsets": [ [ 17, 30 ] ], "normalized": [] }, { "id": "5154", "type": "other_name", "text": [ "myelomonocytic leukemias" ], "offsets": [ [ 67, 91 ] ], "normalized": [] }, { "id": "5155", "type": "other_name", "text": [ "chromosomal 16 abnormalities" ], "offsets": [ [ 117, 145 ] ], "normalized": [] }, { "id": "5156", "type": "other_name", "text": [ "AML M4Eo" ], "offsets": [ [ 174, 182 ] ], "normalized": [] }, { "id": "5157", "type": "other_name", "text": [ "inv(16)(p13q22)" ], "offsets": [ [ 251, 266 ] ], "normalized": [] }, { "id": "5158", "type": "DNA_domain_or_region", "text": [ "CBF beta" ], "offsets": [ [ 268, 276 ] ], "normalized": [] }, { "id": "5159", "type": "DNA_domain_or_region", "text": [ "MYH11" ], "offsets": [ [ 281, 286 ] ], "normalized": [] }, { "id": "5160", "type": "RNA_family_or_group", "text": [ "fusion transcripts" ], "offsets": [ [ 317, 335 ] ], "normalized": [] }, { "id": "5161", "type": "other_name", "text": [ "reverse-transcriptase polymerase chain reaction" ], "offsets": [ [ 339, 386 ] ], "normalized": [] }, { "id": "5162", "type": "other_name", "text": [ "RT-PCR" ], "offsets": [ [ 388, 394 ] ], "normalized": [] }, { "id": "5163", "type": "RNA_family_or_group", "text": [ "CBF beta-MYH11 fusion transcripts" ], "offsets": [ [ 414, 447 ] ], "normalized": [] }, { "id": "5164", "type": "DNA_domain_or_region", "text": [ "CBF beta" ], "offsets": [ [ 414, 422 ] ], "normalized": [] }, { "id": "5165", "type": "DNA_domain_or_region", "text": [ "-MYH11" ], "offsets": [ [ 422, 428 ] ], "normalized": [] }, { "id": "5166", "type": "other_name", "text": [ "RT-PCR" ], "offsets": [ [ 451, 457 ] ], "normalized": [] }, { "id": "5167", "type": "other_name", "text": [ "myelomonocytic leukemias" ], "offsets": [ [ 461, 485 ] ], "normalized": [] }, { "id": "5168", "type": "other_name", "text": [ "eosinophilia" ], "offsets": [ [ 503, 515 ] ], "normalized": [] }, { "id": "5169", "type": "other_name", "text": [ "AML M4Eo" ], "offsets": [ [ 603, 611 ] ], "normalized": [] }, { "id": "5170", "type": "other_name", "text": [ "AML M4" ], "offsets": [ [ 603, 609 ] ], "normalized": [] }, { "id": "5171", "type": "cell_type", "text": [ "atypical abnormal eosinophils" ], "offsets": [ [ 627, 656 ] ], "normalized": [] }, { "id": "5172", "type": "other_name", "text": [ "AML M4" ], "offsets": [ [ 615, 621 ] ], "normalized": [] }, { "id": "5173", "type": "other_name", "text": [ "AML M5" ], "offsets": [ [ 685, 691 ] ], "normalized": [] }, { "id": "5174", "type": "other_name", "text": [ "CMML" ], "offsets": [ [ 695, 699 ] ], "normalized": [] }, { "id": "5175", "type": "other_name", "text": [ "AML M2" ], "offsets": [ [ 707, 713 ] ], "normalized": [] }, { "id": "5176", "type": "other_name", "text": [ "eosinophilia" ], "offsets": [ [ 719, 731 ] ], "normalized": [] }, { "id": "5177", "type": "other_name", "text": [ "AML M4Eo" ], "offsets": [ [ 763, 771 ] ], "normalized": [] }, { "id": "5178", "type": "DNA_domain_or_region", "text": [ "CBF beta" ], "offsets": [ [ 777, 785 ] ], "normalized": [] }, { "id": "5179", "type": "DNA_domain_or_region", "text": [ "-MYH11" ], "offsets": [ [ 785, 791 ] ], "normalized": [] }, { "id": "5180", "type": "other_name", "text": [ "AML M4" ], "offsets": [ [ 821, 827 ] ], "normalized": [] }, { "id": "5181", "type": "other_name", "text": [ "eosinophil abnormalities" ], "offsets": [ [ 845, 869 ] ], "normalized": [] }, { "id": "5182", "type": "other_name", "text": [ "karyotype" ], "offsets": [ [ 886, 895 ] ], "normalized": [] }, { "id": "5183", "type": "other_name", "text": [ "RT-PCR" ], "offsets": [ [ 897, 903 ] ], "normalized": [] }, { "id": "5184", "type": "other_name", "text": [ "fluorescent in situ hybridization" ], "offsets": [ [ 908, 941 ] ], "normalized": [] }, { "id": "5185", "type": "other_name", "text": [ "FISH" ], "offsets": [ [ 943, 947 ] ], "normalized": [] }, { "id": "5186", "type": "other_name", "text": [ "AML M4" ], "offsets": [ [ 968, 974 ] ], "normalized": [] }, { "id": "5187", "type": "cell_type", "text": [ "abnormal eosinophils" ], "offsets": [ [ 983, 1003 ] ], "normalized": [] }, { "id": "5188", "type": "DNA_domain_or_region", "text": [ "CBF beta" ], "offsets": [ [ 1009, 1017 ] ], "normalized": [] }, { "id": "5189", "type": "DNA_domain_or_region", "text": [ "-MYH11" ], "offsets": [ [ 1017, 1023 ] ], "normalized": [] }, { "id": "5190", "type": "DNA_molecule", "text": [ "chromosome 16" ], "offsets": [ [ 1071, 1084 ] ], "normalized": [] }, { "id": "5191", "type": "other_name", "text": [ "classical metaphase analysis" ], "offsets": [ [ 1102, 1130 ] ], "normalized": [] }, { "id": "5192", "type": "other_name", "text": [ "MYH11 genomic rearrangement" ], "offsets": [ [ 1177, 1204 ] ], "normalized": [] }, { "id": "5193", "type": "DNA_domain_or_region", "text": [ "MYH11" ], "offsets": [ [ 1177, 1182 ] ], "normalized": [] }, { "id": "5194", "type": "other_name", "text": [ "leukemias" ], "offsets": [ [ 1224, 1233 ] ], "normalized": [] }, { "id": "5195", "type": "other_name", "text": [ "RT-PCR" ], "offsets": [ [ 1239, 1245 ] ], "normalized": [] }, { "id": "5196", "type": "RNA_family_or_group", "text": [ "CBF beta-MYH11 fusion transcripts" ], "offsets": [ [ 1363, 1396 ] ], "normalized": [] }, { "id": "5197", "type": "DNA_domain_or_region", "text": [ "CBF beta" ], "offsets": [ [ 1363, 1371 ] ], "normalized": [] }, { "id": "5198", "type": "DNA_domain_or_region", "text": [ "-MYH11" ], "offsets": [ [ 1371, 1377 ] ], "normalized": [] }, { "id": "5199", "type": "other_name", "text": [ "AML M4Eo" ], "offsets": [ [ 1444, 1452 ] ], "normalized": [] }, { "id": "5200", "type": "other_name", "text": [ "AML M4" ], "offsets": [ [ 1444, 1450 ] ], "normalized": [] }, { "id": "5201", "type": "other_name", "text": [ "eosinophilic abnormalities" ], "offsets": [ [ 1502, 1528 ] ], "normalized": [] }, { "id": "5202", "type": "other_name", "text": [ "chromosome 16 abnormalities" ], "offsets": [ [ 1583, 1610 ] ], "normalized": [] }, { "id": "5203", "type": "DNA_molecule", "text": [ "chromosome 16" ], "offsets": [ [ 1583, 1596 ] ], "normalized": [] }, { "id": "5204", "type": "other_name", "text": [ "AML M4" ], "offsets": [ [ 1487, 1493 ] ], "normalized": [] }, { "id": "5205", "type": "DNA_domain_or_region", "text": [ "CBF beta" ], "offsets": [ [ 1673, 1681 ] ], "normalized": [] }, { "id": "5206", "type": "RNA_family_or_group", "text": [ "MYH11 transcripts" ], "offsets": [ [ 1682, 1699 ] ], "normalized": [] }, { "id": "5207", "type": "DNA_domain_or_region", "text": [ "MYH11" ], "offsets": [ [ 1682, 1687 ] ], "normalized": [] }, { "id": "5208", "type": "other_name", "text": [ "chromosome 16 abnormalities" ], "offsets": [ [ 1727, 1754 ] ], "normalized": [] }, { "id": "5209", "type": "DNA_molecule", "text": [ "chromosome 16" ], "offsets": [ [ 1727, 1740 ] ], "normalized": [] }, { "id": "5210", "type": "other_name", "text": [ "RT-PCR" ], "offsets": [ [ 1840, 1846 ] ], "normalized": [] }, { "id": "5211", "type": "other_name", "text": [ "FISH" ], "offsets": [ [ 1850, 1854 ] ], "normalized": [] }, { "id": "5212", "type": "other_name", "text": [ "AML M4" ], "offsets": [ [ 1882, 1888 ] ], "normalized": [] }, { "id": "5213", "type": "RNA_family_or_group", "text": [ "fusion transcript" ], "offsets": [ [ 1992, 2009 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "5215", "type": "title", "text": [ "HIV-1 Tat potentiates TNF-induced NF-kappa B activation and cytotoxicity by altering the cellular redox state." ], "offsets": [ [ 0, 110 ] ] }, { "id": "5216", "type": "abstract", "text": [ "This study demonstrates that human immunodeficiency virus type 1 (HIV-1) Tat protein amplifies the activity of tumor necrosis factor (TNF), a cytokine that stimulates HIV-1 replication through activation of NF-kappa B. In HeLa cells stably transfected with the HIV-1 tat gene (HeLa-tat cells), expression of the Tat protein enhanced both TNF-induced activation of NF-kappa B and TNF-mediated cytotoxicity. A similar potentiation of TNF effects was observed in Jurkat T cells and HeLa cells treated with soluble Tat protein. TNF-mediated activation of NF-kappa B and cytotoxicity involves the intracellular formation of reactive oxygen intermediates. Therefore, Tat-mediated effects on the cellular redox state were analyzed. In both T cells and HeLa cells HIV-1 Tat suppressed the expression of Mn-dependent superoxide dismutase (Mn-SOD), a mitochondrial enzyme that is part of the cellular defense system against oxidative stress. Thus, Mn-SOD RNA protein levels and activity were markedly reduced in the presence of Tat. Decreased Mn-SOD expression was associated with decreased levels of glutathione and a lower ratio of reduced:oxidized glutathione. A truncated Tat protein (Tat1-72), known to transactivate the HIV-1 long terminal repeat (LTR), no longer affected Mn-SOD expression, the cellular redox state or TNF-mediated cytotoxicity. Thus, our experiments demonstrate that the C-terminal region of HIV-1 Tat is required to suppress Mn-SOD expression and to induce pro-oxidative conditions reflected by a drop in reduced glutathione (GSH) and the GSH:oxidized GSH (GSSG) ratio. (ABSTRACT TRUNCATED AT 250 WORDS)" ], "offsets": [ [ 111, 1730 ] ] } ]

[ { "id": "5217", "type": "protein_molecule", "text": [ "HIV-1 Tat" ], "offsets": [ [ 0, 9 ] ], "normalized": [] }, { "id": "5218", "type": "virus", "text": [ "HIV-1" ], "offsets": [ [ 0, 5 ] ], "normalized": [] }, { "id": "5219", "type": "other_name", "text": [ "TNF-induced NF-kappa B activation" ], "offsets": [ [ 22, 55 ] ], "normalized": [] }, { "id": "5220", "type": "protein_family_or_group", "text": [ "TNF" ], "offsets": [ [ 22, 25 ] ], "normalized": [] }, { "id": "5221", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 34, 44 ] ], "normalized": [] }, { "id": "5222", "type": "other_name", "text": [ "cytotoxicity" ], "offsets": [ [ 60, 72 ] ], "normalized": [] }, { "id": "5223", "type": "protein_molecule", "text": [ "human immunodeficiency virus type 1 (HIV-1) Tat protein" ], "offsets": [ [ 140, 195 ] ], "normalized": [] }, { "id": "5224", "type": "virus", "text": [ "human immunodeficiency virus type 1" ], "offsets": [ [ 140, 175 ] ], "normalized": [] }, { "id": "5225", "type": "virus", "text": [ "HIV-1" ], "offsets": [ [ 177, 182 ] ], "normalized": [] }, { "id": "5226", "type": "protein_family_or_group", "text": [ "tumor necrosis factor" ], "offsets": [ [ 222, 243 ] ], "normalized": [] }, { "id": "5227", "type": "protein_molecule", "text": [ "TNF" ], "offsets": [ [ 245, 248 ] ], "normalized": [] }, { "id": "5228", "type": "virus", "text": [ "HIV-1" ], "offsets": [ [ 278, 283 ] ], "normalized": [] }, { "id": "5229", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 318, 328 ] ], "normalized": [] }, { "id": "5230", "type": "cell_line", "text": [ "HeLa cells" ], "offsets": [ [ 333, 343 ] ], "normalized": [] }, { "id": "5231", "type": "DNA_domain_or_region", "text": [ "HIV-1 tat gene" ], "offsets": [ [ 372, 386 ] ], "normalized": [] }, { "id": "5232", "type": "virus", "text": [ "HIV-1" ], "offsets": [ [ 372, 377 ] ], "normalized": [] }, { "id": "5233", "type": "cell_line", "text": [ "HeLa-tat cells" ], "offsets": [ [ 388, 402 ] ], "normalized": [] }, { "id": "5234", "type": "protein_molecule", "text": [ "Tat protein" ], "offsets": [ [ 423, 434 ] ], "normalized": [] }, { "id": "5235", "type": "other_name", "text": [ "TNF-induced activation" ], "offsets": [ [ 449, 471 ] ], "normalized": [] }, { "id": "5236", "type": "protein_molecule", "text": [ "TNF" ], "offsets": [ [ 449, 452 ] ], "normalized": [] }, { "id": "5237", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 475, 485 ] ], "normalized": [] }, { "id": "5238", "type": "other_name", "text": [ "TNF-mediated cytotoxicity" ], "offsets": [ [ 490, 515 ] ], "normalized": [] }, { "id": "5239", "type": "protein_molecule", "text": [ "TNF" ], "offsets": [ [ 490, 493 ] ], "normalized": [] }, { "id": "5240", "type": "protein_molecule", "text": [ "TNF" ], "offsets": [ [ 543, 546 ] ], "normalized": [] }, { "id": "5241", "type": "cell_line", "text": [ "HeLa cells" ], "offsets": [ [ 590, 600 ] ], "normalized": [] }, { "id": "5242", "type": "protein_molecule", "text": [ "Tat protein" ], "offsets": [ [ 622, 633 ] ], "normalized": [] }, { "id": "5243", "type": "protein_molecule", "text": [ "TNF" ], "offsets": [ [ 635, 638 ] ], "normalized": [] }, { "id": "5244", "type": "protein_molecule", "text": [ "NF-kappa B" ], "offsets": [ [ 662, 672 ] ], "normalized": [] }, { "id": "5245", "type": "inorganic", "text": [ "reactive oxygen intermediates" ], "offsets": [ [ 730, 759 ] ], "normalized": [] }, { "id": "5246", "type": "other_name", "text": [ "Tat-mediated effects" ], "offsets": [ [ 772, 792 ] ], "normalized": [] }, { "id": "5247", "type": "protein_molecule", "text": [ "Tat" ], "offsets": [ [ 772, 775 ] ], "normalized": [] }, { "id": "5248", "type": "other_name", "text": [ "cellular redox state" ], "offsets": [ [ 800, 820 ] ], "normalized": [] }, { "id": "5249", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 844, 851 ] ], "normalized": [] }, { "id": "5250", "type": "cell_line", "text": [ "HeLa cells" ], "offsets": [ [ 856, 866 ] ], "normalized": [] }, { "id": "5251", "type": "protein_molecule", "text": [ "HIV-1 Tat" ], "offsets": [ [ 867, 876 ] ], "normalized": [] }, { "id": "5252", "type": "virus", "text": [ "HIV-1" ], "offsets": [ [ 867, 872 ] ], "normalized": [] }, { "id": "5253", "type": "protein_molecule", "text": [ "Mn-dependent superoxide dismutase" ], "offsets": [ [ 906, 939 ] ], "normalized": [] }, { "id": "5254", "type": "protein_molecule", "text": [ "Mn-SOD" ], "offsets": [ [ 941, 947 ] ], "normalized": [] }, { "id": "5255", "type": "protein_molecule", "text": [ "mitochondrial enzyme" ], "offsets": [ [ 952, 972 ] ], "normalized": [] }, { "id": "5256", "type": "other_name", "text": [ "oxidative stress" ], "offsets": [ [ 1025, 1041 ] ], "normalized": [] }, { "id": "5257", "type": "other_name", "text": [ "Mn-SOD RNA protein levels" ], "offsets": [ [ 1049, 1074 ] ], "normalized": [] }, { "id": "5258", "type": "protein_molecule", "text": [ "Mn-SOD" ], "offsets": [ [ 1049, 1055 ] ], "normalized": [] }, { "id": "5259", "type": "protein_molecule", "text": [ "Tat" ], "offsets": [ [ 1129, 1132 ] ], "normalized": [] }, { "id": "5260", "type": "other_name", "text": [ "Mn-SOD expression" ], "offsets": [ [ 1144, 1161 ] ], "normalized": [] }, { "id": "5261", "type": "protein_molecule", "text": [ "Mn-SOD" ], "offsets": [ [ 1144, 1150 ] ], "normalized": [] }, { "id": "5262", "type": "peptide", "text": [ "glutathione" ], "offsets": [ [ 1202, 1213 ] ], "normalized": [] }, { "id": "5263", "type": "peptide", "text": [ "glutathione" ], "offsets": [ [ 1252, 1263 ] ], "normalized": [] }, { "id": "5264", "type": "protein_molecule", "text": [ "Tat protein" ], "offsets": [ [ 1277, 1288 ] ], "normalized": [] }, { "id": "5265", "type": "protein_molecule", "text": [ "Tat" ], "offsets": [ [ 1277, 1280 ] ], "normalized": [] }, { "id": "5266", "type": "protein_molecule", "text": [ "Tat1-72" ], "offsets": [ [ 1290, 1297 ] ], "normalized": [] }, { "id": "5267", "type": "DNA_domain_or_region", "text": [ "HIV-1 long terminal repeat" ], "offsets": [ [ 1327, 1353 ] ], "normalized": [] }, { "id": "5268", "type": "virus", "text": [ "HIV-1" ], "offsets": [ [ 1327, 1332 ] ], "normalized": [] }, { "id": "5269", "type": "DNA_domain_or_region", "text": [ "LTR" ], "offsets": [ [ 1355, 1358 ] ], "normalized": [] }, { "id": "5270", "type": "other_name", "text": [ "Mn-SOD expression" ], "offsets": [ [ 1380, 1397 ] ], "normalized": [] }, { "id": "5271", "type": "protein_molecule", "text": [ "Mn-SOD" ], "offsets": [ [ 1380, 1386 ] ], "normalized": [] }, { "id": "5272", "type": "other_name", "text": [ "cellular redox state" ], "offsets": [ [ 1403, 1423 ] ], "normalized": [] }, { "id": "5273", "type": "other_name", "text": [ "TNF-mediated cytotoxicity" ], "offsets": [ [ 1427, 1452 ] ], "normalized": [] }, { "id": "5274", "type": "protein_molecule", "text": [ "TNF" ], "offsets": [ [ 1427, 1430 ] ], "normalized": [] }, { "id": "5275", "type": "protein_domain_or_region", "text": [ "C-terminal region" ], "offsets": [ [ 1497, 1514 ] ], "normalized": [] }, { "id": "5276", "type": "protein_molecule", "text": [ "HIV-1 Tat" ], "offsets": [ [ 1518, 1527 ] ], "normalized": [] }, { "id": "5277", "type": "virus", "text": [ "HIV-1" ], "offsets": [ [ 1518, 1523 ] ], "normalized": [] }, { "id": "5278", "type": "protein_molecule", "text": [ "Tat" ], "offsets": [ [ 1524, 1527 ] ], "normalized": [] }, { "id": "5279", "type": "other_name", "text": [ "Mn-SOD expression" ], "offsets": [ [ 1552, 1569 ] ], "normalized": [] }, { "id": "5280", "type": "protein_molecule", "text": [ "Mn-SOD" ], "offsets": [ [ 1552, 1558 ] ], "normalized": [] }, { "id": "5281", "type": "peptide", "text": [ "glutathione" ], "offsets": [ [ 1640, 1651 ] ], "normalized": [] }, { "id": "5282", "type": "protein_molecule", "text": [ "GSH" ], "offsets": [ [ 1653, 1656 ] ], "normalized": [] }, { "id": "5283", "type": "other_name", "text": [ "GSH:oxidized GSH (GSSG) ratio" ], "offsets": [ [ 1666, 1695 ] ], "normalized": [] }, { "id": "5284", "type": "peptide", "text": [ "GSH" ], "offsets": [ [ 1653, 1656 ] ], "normalized": [] }, { "id": "5285", "type": "peptide", "text": [ "GSSG" ], "offsets": [ [ 1684, 1688 ] ], "normalized": [] } ]

[]

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[ { "id": "5287", "type": "title", "text": [ "The use of glucocorticoids in acute lymphoblastic leukemia of childhood. Molecular, cellular, and clinical considerations." ], "offsets": [ [ 0, 122 ] ] }, { "id": "5288", "type": "abstract", "text": [ "Glucocorticoids have been included in almost all treatment regimens for childhood acute lymphoblastic leukemia for decades. However, optimal agents, doses, and/or schedules have yet to be defined despite extensive clinical application. New data on the pharmacokinetics, pharmacodynamics, and molecular mechanisms of action of glucocorticoids have suggested alternative approaches in ALL. These suggest that prolonged, i.e. 28 day, glucocorticoid therapy may be unnecessary as exposure to glucocorticoid induces down-regulation of glucocorticoid receptors. Dexamethasone may be superior to prednisone in conventional equi-effective doses. Blast sensitivity to glucocorticoids correlates closely with sensitivity to other, putatively non-cross-resisting agents and with outcome after multi-agent therapy, suggesting overlapping mechanisms of action, and focusing attention on the determinants of the threshold for apoptosis. Increasing success in the treatment of childhood acute lymphoblastic leukemia has led to increasing awareness of avascular necrosis of bone as a potentially disabling sequela of glucocorticoid therapy, especially in adolescent and young adult patients." ], "offsets": [ [ 123, 1298 ] ] } ]

[ { "id": "5289", "type": "lipid", "text": [ "glucocorticoids" ], "offsets": [ [ 11, 26 ] ], "normalized": [] }, { "id": "5290", "type": "other_name", "text": [ "acute lymphoblastic leukemia" ], "offsets": [ [ 30, 58 ] ], "normalized": [] }, { "id": "5291", "type": "lipid", "text": [ "Glucocorticoids" ], "offsets": [ [ 123, 138 ] ], "normalized": [] }, { "id": "5292", "type": "other_name", "text": [ "childhood acute lymphoblastic leukemia" ], "offsets": [ [ 195, 233 ] ], "normalized": [] }, { "id": "5293", "type": "other_name", "text": [ "pharmacokinetics" ], "offsets": [ [ 375, 391 ] ], "normalized": [] }, { "id": "5294", "type": "other_name", "text": [ "pharmacodynamics" ], "offsets": [ [ 393, 409 ] ], "normalized": [] }, { "id": "5295", "type": "lipid", "text": [ "glucocorticoids" ], "offsets": [ [ 449, 464 ] ], "normalized": [] }, { "id": "5296", "type": "other_name", "text": [ "ALL" ], "offsets": [ [ 506, 509 ] ], "normalized": [] }, { "id": "5297", "type": "other_name", "text": [ "glucocorticoid therapy" ], "offsets": [ [ 554, 576 ] ], "normalized": [] }, { "id": "5298", "type": "lipid", "text": [ "glucocorticoid" ], "offsets": [ [ 554, 568 ] ], "normalized": [] }, { "id": "5299", "type": "lipid", "text": [ "glucocorticoid" ], "offsets": [ [ 611, 625 ] ], "normalized": [] }, { "id": "5300", "type": "protein_family_or_group", "text": [ "glucocorticoid receptors" ], "offsets": [ [ 653, 677 ] ], "normalized": [] }, { "id": "5301", "type": "lipid", "text": [ "glucocorticoid" ], "offsets": [ [ 653, 667 ] ], "normalized": [] }, { "id": "5302", "type": "lipid", "text": [ "Dexamethasone" ], "offsets": [ [ 679, 692 ] ], "normalized": [] }, { "id": "5303", "type": "lipid", "text": [ "glucocorticoids" ], "offsets": [ [ 782, 797 ] ], "normalized": [] }, { "id": "5304", "type": "other_name", "text": [ "multi-agent therapy" ], "offsets": [ [ 905, 924 ] ], "normalized": [] }, { "id": "5305", "type": "other_name", "text": [ "apoptosis" ], "offsets": [ [ 1035, 1044 ] ], "normalized": [] }, { "id": "5306", "type": "other_name", "text": [ "childhood acute lymphoblastic leukemia" ], "offsets": [ [ 1085, 1123 ] ], "normalized": [] }, { "id": "5307", "type": "other_name", "text": [ "avascular necrosis" ], "offsets": [ [ 1159, 1177 ] ], "normalized": [] }, { "id": "5308", "type": "tissue", "text": [ "bone" ], "offsets": [ [ 1181, 1185 ] ], "normalized": [] }, { "id": "5309", "type": "other_name", "text": [ "glucocorticoid therapy" ], "offsets": [ [ 1224, 1246 ] ], "normalized": [] }, { "id": "5310", "type": "lipid", "text": [ "glucocorticoid" ], "offsets": [ [ 1224, 1238 ] ], "normalized": [] }, { "id": "5311", "type": "(AND multi_cell multi_cell)", "text": [ "adolescent and young adult patients" ], "offsets": [ [ 1262, 1297 ] ], "normalized": [] }, { "id": "5312", "type": "", "text": [ "adolescent" ], "offsets": [ [ 1262, 1272 ] ], "normalized": [] }, { "id": "5313", "type": "", "text": [ "young adult" ], "offsets": [ [ 1277, 1288 ] ], "normalized": [] }, { "id": "5314", "type": "", "text": [ "patients" ], "offsets": [ [ 1289, 1297 ] ], "normalized": [] } ]

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[ { "id": "5316", "type": "title", "text": [ "Epstein-Barr virus nuclear protein 2 transactivation of the latent membrane protein 1 promoter is mediated by J kappa and PU.1." ], "offsets": [ [ 0, 127 ] ] }, { "id": "5317", "type": "abstract", "text": [ "Expression of the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP-1) oncogene is regulated by the EBV nuclear protein 2 (EBNA-2) transactivator. EBNA-2 is known to interact with the cellular DNA-binding protein J kappa and is recruited to promoters containing the GTGGGAA J kappa recognition sequence. The minimal EBNA-2-responsive LMP-1 promoter includes one J kappa-binding site, and we now show that mutation of that site, such that J kappa cannot bind, reduces EBNA-2 responsiveness by 60%. To identify other factors which interact with the LMP-1 EBNA-2 response element (E2RE), a -236/-145 minimal E2RE was used as a probe in an electrophoretic mobility shift assay. The previously characterized factors J kappa, PU.1, and AML1 bind to the LMP-1 E2RE, along with six other unidentified factors (LBF2 to LBF7). Binding sites were mapped for each factor. LBF4 is B- and T-cell specific and recognizes the PU.1 GGAA core sequence as shown by methylation interference. LBF4 has a molecular mass of 105 kDa and is probably unrelated to PU.1. LBF2 was found only in epithelial cell lines, whereas LBF3, LBF5, LBF6, and LBF7 were not cell type specific. Mutations of the AML1- or LBF4-binding sites had no effect on EBNA-2 transactivation, whereas mutation of the PU.1-binding site completely eliminated EBNA-2 responses. A gst-EBNA-2 fusion protein specifically depleted PU.1 from nuclear extracts and bound in vitro translated PU.1, providing biochemical evidence for a direct EBNA-2-PU.1 interaction. Thus, EBNA-2 transactivation of the LMP-1 promoter is dependent on interaction with at least two distinct sequence-specific DNA-binding proteins, J kappa and PU.1. LBF3, LBF5, LBF6, or LBF7 may also be involved, since their binding sites also contribute to EBNA-2 responsiveness." ], "offsets": [ [ 128, 1917 ] ] } ]

[ { "id": "5318", "type": "other_name", "text": [ "Epstein-Barr virus nuclear protein 2 transactivation" ], "offsets": [ [ 0, 52 ] ], "normalized": [] }, { "id": "5319", "type": "protein_molecule", "text": [ "Epstein-Barr virus nuclear protein 2" ], "offsets": [ [ 0, 36 ] ], "normalized": [] }, { "id": "5320", "type": "virus", "text": [ "Epstein-Barr virus" ], "offsets": [ [ 0, 18 ] ], "normalized": [] }, { "id": "5321", "type": "DNA_domain_or_region", "text": [ "latent membrane protein 1 promoter" ], "offsets": [ [ 60, 94 ] ], "normalized": [] }, { "id": "5322", "type": "protein_molecule", "text": [ "J kappa" ], "offsets": [ [ 110, 117 ] ], "normalized": [] }, { "id": "5323", "type": "protein_molecule", "text": [ "PU.1" ], "offsets": [ [ 122, 126 ] ], "normalized": [] }, { "id": "5324", "type": "DNA_domain_or_region", "text": [ "Epstein-Barr virus (EBV) latent membrane protein 1 (LMP-1) oncogene" ], "offsets": [ [ 146, 213 ] ], "normalized": [] }, { "id": "5325", "type": "virus", "text": [ "Epstein-Barr virus" ], "offsets": [ [ 146, 164 ] ], "normalized": [] }, { "id": "5326", "type": "virus", "text": [ "EBV" ], "offsets": [ [ 166, 169 ] ], "normalized": [] }, { "id": "5327", "type": "protein_family_or_group", "text": [ "latent membrane protein 1" ], "offsets": [ [ 171, 196 ] ], "normalized": [] }, { "id": "5328", "type": "protein_molecule", "text": [ "LMP-1" ], "offsets": [ [ 198, 203 ] ], "normalized": [] }, { "id": "5329", "type": "protein_molecule", "text": [ "EBV nuclear protein 2 (EBNA-2) transactivator" ], "offsets": [ [ 234, 279 ] ], "normalized": [] }, { "id": "5330", "type": "protein_molecule", "text": [ "EBNA-2" ], "offsets": [ [ 257, 263 ] ], "normalized": [] }, { "id": "5331", "type": "protein_molecule", "text": [ "EBNA-2" ], "offsets": [ [ 281, 287 ] ], "normalized": [] }, { "id": "5332", "type": "protein_family_or_group", "text": [ "cellular DNA-binding protein" ], "offsets": [ [ 318, 346 ] ], "normalized": [] }, { "id": "5333", "type": "protein_molecule", "text": [ "J kappa" ], "offsets": [ [ 347, 354 ] ], "normalized": [] }, { "id": "5334", "type": "DNA_family_or_group", "text": [ "promoters" ], "offsets": [ [ 375, 384 ] ], "normalized": [] }, { "id": "5335", "type": "polynucleotide", "text": [ "GTGGGAA" ], "offsets": [ [ 400, 407 ] ], "normalized": [] }, { "id": "5336", "type": "DNA_domain_or_region", "text": [ "J kappa recognition sequence" ], "offsets": [ [ 408, 436 ] ], "normalized": [] }, { "id": "5337", "type": "protein_molecule", "text": [ "J kappa" ], "offsets": [ [ 408, 415 ] ], "normalized": [] }, { "id": "5338", "type": "DNA_domain_or_region", "text": [ "minimal EBNA-2-responsive LMP-1 promoter" ], "offsets": [ [ 442, 482 ] ], "normalized": [] }, { "id": "5339", "type": "protein_molecule", "text": [ "EBNA-2" ], "offsets": [ [ 450, 456 ] ], "normalized": [] }, { "id": "5340", "type": "DNA_domain_or_region", "text": [ "J kappa-binding site" ], "offsets": [ [ 496, 516 ] ], "normalized": [] }, { "id": "5341", "type": "protein_molecule", "text": [ "J kappa" ], "offsets": [ [ 496, 503 ] ], "normalized": [] }, { "id": "5342", "type": "protein_molecule", "text": [ "J kappa" ], "offsets": [ [ 572, 579 ] ], "normalized": [] }, { "id": "5343", "type": "protein_molecule", "text": [ "EBNA-2" ], "offsets": [ [ 601, 607 ] ], "normalized": [] }, { "id": "5344", "type": "DNA_domain_or_region", "text": [ "LMP-1 EBNA-2 response element" ], "offsets": [ [ 681, 710 ] ], "normalized": [] }, { "id": "5345", "type": "protein_molecule", "text": [ "EBNA-2" ], "offsets": [ [ 687, 693 ] ], "normalized": [] }, { "id": "5346", "type": "DNA_domain_or_region", "text": [ "E2RE" ], "offsets": [ [ 712, 716 ] ], "normalized": [] }, { "id": "5347", "type": "DNA_molecule", "text": [ "-236/-145 minimal E2RE" ], "offsets": [ [ 721, 743 ] ], "normalized": [] }, { "id": "5348", "type": "other_name", "text": [ "electrophoretic mobility shift assay" ], "offsets": [ [ 770, 806 ] ], "normalized": [] }, { "id": "5349", "type": "protein_molecule", "text": [ "J kappa" ], "offsets": [ [ 845, 852 ] ], "normalized": [] }, { "id": "5350", "type": "protein_molecule", "text": [ "PU.1" ], "offsets": [ [ 854, 858 ] ], "normalized": [] }, { "id": "5351", "type": "protein_molecule", "text": [ "AML1" ], "offsets": [ [ 864, 868 ] ], "normalized": [] }, { "id": "5352", "type": "DNA_domain_or_region", "text": [ "LMP-1 E2RE" ], "offsets": [ [ 881, 891 ] ], "normalized": [] }, { "id": "5353", "type": "protein_molecule", "text": [ "LBF2" ], "offsets": [ [ 936, 940 ] ], "normalized": [] }, { "id": "5354", "type": "protein_molecule", "text": [ "LBF7" ], "offsets": [ [ 944, 948 ] ], "normalized": [] }, { "id": "5355", "type": "protein_molecule", "text": [ "LBF4" ], "offsets": [ [ 994, 998 ] ], "normalized": [] }, { "id": "5356", "type": "DNA_domain_or_region", "text": [ "PU.1 GGAA core sequence" ], "offsets": [ [ 1044, 1067 ] ], "normalized": [] }, { "id": "5357", "type": "protein_molecule", "text": [ "PU.1" ], "offsets": [ [ 1044, 1048 ] ], "normalized": [] }, { "id": "5358", "type": "other_name", "text": [ "methylation interference" ], "offsets": [ [ 1080, 1104 ] ], "normalized": [] }, { "id": "5359", "type": "protein_molecule", "text": [ "LBF4" ], "offsets": [ [ 1106, 1110 ] ], "normalized": [] }, { "id": "5360", "type": "protein_molecule", "text": [ "PU.1" ], "offsets": [ [ 1172, 1176 ] ], "normalized": [] }, { "id": "5361", "type": "protein_molecule", "text": [ "LBF2" ], "offsets": [ [ 1178, 1182 ] ], "normalized": [] }, { "id": "5362", "type": "cell_line", "text": [ "epithelial cell lines" ], "offsets": [ [ 1201, 1222 ] ], "normalized": [] }, { "id": "5363", "type": "protein_molecule", "text": [ "LBF3" ], "offsets": [ [ 1232, 1236 ] ], "normalized": [] }, { "id": "5364", "type": "protein_molecule", "text": [ "LBF5" ], "offsets": [ [ 1238, 1242 ] ], "normalized": [] }, { "id": "5365", "type": "protein_molecule", "text": [ "LBF6" ], "offsets": [ [ 1244, 1248 ] ], "normalized": [] }, { "id": "5366", "type": "protein_molecule", "text": [ "LBF7" ], "offsets": [ [ 1254, 1258 ] ], "normalized": [] }, { "id": "5367", "type": "(OR DNA_domain_or_region DNA_domain_or_region)", "text": [ "AML1- or LBF4-binding sites" ], "offsets": [ [ 1305, 1332 ] ], "normalized": [] }, { "id": "5368", "type": "", "text": [ "AML1-" ], "offsets": [ [ 1305, 1310 ] ], "normalized": [] }, { "id": "5369", "type": "", "text": [ "LBF4-" ], "offsets": [ [ 1314, 1319 ] ], "normalized": [] }, { "id": "5370", "type": "", "text": [ "binding sites" ], "offsets": [ [ 1319, 1332 ] ], "normalized": [] }, { "id": "5371", "type": "other_name", "text": [ "EBNA-2 transactivation" ], "offsets": [ [ 1350, 1372 ] ], "normalized": [] }, { "id": "5372", "type": "protein_molecule", "text": [ "EBNA-2" ], "offsets": [ [ 1350, 1356 ] ], "normalized": [] }, { "id": "5373", "type": "DNA_domain_or_region", "text": [ "PU.1-binding site" ], "offsets": [ [ 1398, 1415 ] ], "normalized": [] }, { "id": "5374", "type": "protein_molecule", "text": [ "PU.1" ], "offsets": [ [ 1398, 1402 ] ], "normalized": [] }, { "id": "5375", "type": "other_name", "text": [ "EBNA-2 responses" ], "offsets": [ [ 1438, 1454 ] ], "normalized": [] }, { "id": "5376", "type": "protein_molecule", "text": [ "EBNA-2" ], "offsets": [ [ 1438, 1444 ] ], "normalized": [] }, { "id": "5377", "type": "protein_molecule", "text": [ "gst-EBNA-2 fusion protein" ], "offsets": [ [ 1458, 1483 ] ], "normalized": [] }, { "id": "5378", "type": "protein_molecule", "text": [ "EBNA-2" ], "offsets": [ [ 1462, 1468 ] ], "normalized": [] }, { "id": "5379", "type": "protein_molecule", "text": [ "PU.1" ], "offsets": [ [ 1506, 1510 ] ], "normalized": [] }, { "id": "5380", "type": "cell_component", "text": [ "nuclear extracts" ], "offsets": [ [ 1516, 1532 ] ], "normalized": [] }, { "id": "5381", "type": "protein_molecule", "text": [ "PU.1" ], "offsets": [ [ 1563, 1567 ] ], "normalized": [] }, { "id": "5382", "type": "protein_molecule", "text": [ "EBNA-2" ], "offsets": [ [ 1613, 1619 ] ], "normalized": [] }, { "id": "5383", "type": "protein_molecule", "text": [ "-PU.1" ], "offsets": [ [ 1619, 1624 ] ], "normalized": [] }, { "id": "5384", "type": "protein_molecule", "text": [ "EBNA-2" ], "offsets": [ [ 1644, 1650 ] ], "normalized": [] }, { "id": "5385", "type": "DNA_domain_or_region", "text": [ "LMP-1 promoter" ], "offsets": [ [ 1674, 1688 ] ], "normalized": [] }, { "id": "5386", "type": "protein_family_or_group", "text": [ "DNA-binding proteins" ], "offsets": [ [ 1762, 1782 ] ], "normalized": [] }, { "id": "5387", "type": "protein_molecule", "text": [ "J kappa" ], "offsets": [ [ 1784, 1791 ] ], "normalized": [] }, { "id": "5388", "type": "protein_molecule", "text": [ "PU.1" ], "offsets": [ [ 1796, 1800 ] ], "normalized": [] }, { "id": "5389", "type": "protein_molecule", "text": [ "LBF3" ], "offsets": [ [ 1802, 1806 ] ], "normalized": [] }, { "id": "5390", "type": "protein_molecule", "text": [ "LBF5" ], "offsets": [ [ 1808, 1812 ] ], "normalized": [] }, { "id": "5391", "type": "protein_molecule", "text": [ "LBF6" ], "offsets": [ [ 1814, 1818 ] ], "normalized": [] }, { "id": "5392", "type": "protein_molecule", "text": [ "LBF7" ], "offsets": [ [ 1823, 1827 ] ], "normalized": [] }, { "id": "5393", "type": "other_name", "text": [ "EBNA-2 responsiveness" ], "offsets": [ [ 1895, 1916 ] ], "normalized": [] }, { "id": "5394", "type": "protein_molecule", "text": [ "EBNA-2" ], "offsets": [ [ 1895, 1901 ] ], "normalized": [] } ]

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[]

[ { "id": "5396", "type": "title", "text": [ "Lymphocyte glucocorticoid receptor: predictor of sertraline response in adolescent major depressive disorder (MDD)." ], "offsets": [ [ 0, 115 ] ] }, { "id": "5397", "type": "abstract", "text": [ "Major depressive disorder (MDD) in adolescents demonstrates resistance to tricyclic antidepressants and absence of hypercortisolemia. The efficacy of serotonin reuptake inhibitors (SRIs) is uncertain, and response predictors are unavailable. Abnormal fast feedback and negative feedback of the hypothalamic-pituitary-adrenal axis implicates a dampened limbic-hippocampal glucocorticoid type II receptor (GCII). We hypothesized that lymphocyte GCII is altered in adolescent MDD and could serve as a marker for response to SRIs. In an open-label study, adolescents (n = 20) meeting DSM-III-R criteria for MDD showed baseline lymphocyte GCII sites per cell (sites/cell) values of 793 +/- 106 versus 2,563 +/- 499 (+/- SEM) for matched controls (n = 18) (t = 3.5; df = 36; p < .001). GCII was bimodally distributed, with SRI responders differing from nonresponders (t = 3.9; df = 14; p < .001). GCII accurately classified 90 percent of sertraline responders and 80 percent of nonresponders. Only SRI responders showed GCII sites/cell upregulated after 6 weeks of treatment (t = 2.1, df = 10; p < .05)." ], "offsets": [ [ 116, 1213 ] ] } ]

[ { "id": "5398", "type": "protein_family_or_group", "text": [ "Lymphocyte glucocorticoid receptor" ], "offsets": [ [ 0, 34 ] ], "normalized": [] }, { "id": "5399", "type": "lipid", "text": [ "glucocorticoid" ], "offsets": [ [ 11, 25 ] ], "normalized": [] }, { "id": "5400", "type": "other_name", "text": [ "sertraline response" ], "offsets": [ [ 49, 68 ] ], "normalized": [] }, { "id": "5401", "type": "other_organic_compound", "text": [ "sertraline" ], "offsets": [ [ 49, 59 ] ], "normalized": [] }, { "id": "5402", "type": "other_name", "text": [ "adolescent major depressive disorder" ], "offsets": [ [ 72, 108 ] ], "normalized": [] }, { "id": "5403", "type": "other_name", "text": [ "MDD" ], "offsets": [ [ 110, 113 ] ], "normalized": [] }, { "id": "5404", "type": "other_name", "text": [ "Major depressive disorder" ], "offsets": [ [ 116, 141 ] ], "normalized": [] }, { "id": "5405", "type": "other_name", "text": [ "MDD" ], "offsets": [ [ 143, 146 ] ], "normalized": [] }, { "id": "5406", "type": "multi_cell", "text": [ "adolescents" ], "offsets": [ [ 151, 162 ] ], "normalized": [] }, { "id": "5407", "type": "other_organic_compound", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 190, 215 ] ], "normalized": [] }, { "id": "5408", "type": "other_name", "text": [ "hypercortisolemia" ], "offsets": [ [ 231, 248 ] ], "normalized": [] }, { "id": "5409", "type": "other_organic_compound", "text": [ "serotonin reuptake inhibitors" ], "offsets": [ [ 266, 295 ] ], "normalized": [] }, { "id": "5410", "type": "other_organic_compound", "text": [ "SRIs" ], "offsets": [ [ 297, 301 ] ], "normalized": [] }, { "id": "5411", "type": "body_part", "text": [ "hypothalamic-pituitary-adrenal axis" ], "offsets": [ [ 410, 445 ] ], "normalized": [] }, { "id": "5412", "type": "protein_molecule", "text": [ "limbic-hippocampal glucocorticoid type II receptor" ], "offsets": [ [ 468, 518 ] ], "normalized": [] }, { "id": "5413", "type": "lipid", "text": [ "glucocorticoid" ], "offsets": [ [ 487, 501 ] ], "normalized": [] }, { "id": "5414", "type": "protein_molecule", "text": [ "GCII" ], "offsets": [ [ 520, 524 ] ], "normalized": [] }, { "id": "5415", "type": "protein_molecule", "text": [ "lymphocyte GCII" ], "offsets": [ [ 548, 563 ] ], "normalized": [] }, { "id": "5416", "type": "protein_molecule", "text": [ "GCII" ], "offsets": [ [ 559, 563 ] ], "normalized": [] }, { "id": "5417", "type": "other_name", "text": [ "MDD" ], "offsets": [ [ 589, 592 ] ], "normalized": [] }, { "id": "5418", "type": "other_organic_compound", "text": [ "SRIs" ], "offsets": [ [ 637, 641 ] ], "normalized": [] }, { "id": "5419", "type": "multi_cell", "text": [ "adolescents" ], "offsets": [ [ 667, 678 ] ], "normalized": [] }, { "id": "5420", "type": "other_name", "text": [ "DSM-III-R criteria" ], "offsets": [ [ 696, 714 ] ], "normalized": [] }, { "id": "5421", "type": "other_name", "text": [ "MDD" ], "offsets": [ [ 719, 722 ] ], "normalized": [] }, { "id": "5422", "type": "protein_family_or_group", "text": [ "lymphocyte GCII sites" ], "offsets": [ [ 739, 760 ] ], "normalized": [] }, { "id": "5423", "type": "protein_molecule", "text": [ "GCII" ], "offsets": [ [ 750, 754 ] ], "normalized": [] }, { "id": "5424", "type": "protein_molecule", "text": [ "GCII" ], "offsets": [ [ 896, 900 ] ], "normalized": [] }, { "id": "5425", "type": "other_organic_compound", "text": [ "SRI" ], "offsets": [ [ 933, 936 ] ], "normalized": [] }, { "id": "5426", "type": "protein_molecule", "text": [ "GCII" ], "offsets": [ [ 1007, 1011 ] ], "normalized": [] }, { "id": "5427", "type": "other_organic_compound", "text": [ "sertraline" ], "offsets": [ [ 1048, 1058 ] ], "normalized": [] }, { "id": "5428", "type": "other_organic_compound", "text": [ "SRI" ], "offsets": [ [ 1108, 1111 ] ], "normalized": [] }, { "id": "5429", "type": "protein_molecule", "text": [ "GCII" ], "offsets": [ [ 1130, 1134 ] ], "normalized": [] } ]

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[ { "id": "5431", "type": "title", "text": [ "The role of NFATp in cyclosporin A-sensitive tumor necrosis factor-alpha gene transcription." ], "offsets": [ [ 0, 92 ] ] }, { "id": "5432", "type": "abstract", "text": [ "The tumor necrosis factor-alpha (TNF alpha) gene is an immediate early gene in activated T cells, in that it is rapidly induced without a requirement for protein synthesis. Maximal induction of TNF alpha mRNA can be induced by treatment of T cells with calcium ionophores alone, via a calcineurin-dependent process that is blocked by cyclosporin A. We have previously identified a promoter element, kappa 3, that is required for calcium-stimulated, cyclosporin A-sensitive induction of the TNF alpha gene in activated T cells. Here, we demonstrate that the kappa 3 binding factor contains NFATp, a cyclosporin-sensitive DNA-binding protein required for interleukin-2 gene transcription. NFATp binds to two sites within the kappa 3 element, and occupancy of both sites is required for TNF alpha gene induction. Thus, although the kappa 3 element has little sequence similarity to other NFATp-binding sites, it appears to function as a cyclosporin-sensitive promoter element in T cells by virtue of its ability to bind NFATp. The involvement of NFATp in transcriptional activation of both the interleukin-2 and TNF alpha genes suggests that this factor plays an important role in the coordinate induction of multiple cytokine genes, starting at the earliest stages of T cell activation." ], "offsets": [ [ 93, 1377 ] ] } ]

[ { "id": "5433", "type": "protein_molecule", "text": [ "NFATp" ], "offsets": [ [ 12, 17 ] ], "normalized": [] }, { "id": "5434", "type": "other_name", "text": [ "cyclosporin A-sensitive tumor necrosis factor-alpha gene transcription" ], "offsets": [ [ 21, 91 ] ], "normalized": [] }, { "id": "5435", "type": "DNA_domain_or_region", "text": [ "cyclosporin A-sensitive tumor necrosis factor-alpha gene" ], "offsets": [ [ 21, 77 ] ], "normalized": [] }, { "id": "5436", "type": "protein_molecule", "text": [ "cyclosporin A-sensitive tumor necrosis factor" ], "offsets": [ [ 21, 66 ] ], "normalized": [] }, { "id": "5437", "type": "DNA_domain_or_region", "text": [ "tumor necrosis factor-alpha (TNF alpha) gene" ], "offsets": [ [ 97, 141 ] ], "normalized": [] }, { "id": "5438", "type": "protein_molecule", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 97, 124 ] ], "normalized": [] }, { "id": "5439", "type": "protein_molecule", "text": [ "TNF" ], "offsets": [ [ 126, 129 ] ], "normalized": [] }, { "id": "5440", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 182, 189 ] ], "normalized": [] }, { "id": "5441", "type": "other_name", "text": [ "protein synthesis" ], "offsets": [ [ 247, 264 ] ], "normalized": [] }, { "id": "5442", "type": "RNA_molecule", "text": [ "TNF alpha mRNA" ], "offsets": [ [ 287, 301 ] ], "normalized": [] }, { "id": "5443", "type": "protein_molecule", "text": [ "TNF" ], "offsets": [ [ 287, 290 ] ], "normalized": [] }, { "id": "5444", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 333, 340 ] ], "normalized": [] }, { "id": "5445", "type": "other_organic_compound", "text": [ "calcium ionophores" ], "offsets": [ [ 346, 364 ] ], "normalized": [] }, { "id": "5446", "type": "other_name", "text": [ "calcineurin-dependent process" ], "offsets": [ [ 378, 407 ] ], "normalized": [] }, { "id": "5447", "type": "protein_molecule", "text": [ "calcineurin" ], "offsets": [ [ 378, 389 ] ], "normalized": [] }, { "id": "5448", "type": "other_organic_compound", "text": [ "cyclosporin A" ], "offsets": [ [ 427, 440 ] ], "normalized": [] }, { "id": "5449", "type": "DNA_domain_or_region", "text": [ "promoter element" ], "offsets": [ [ 474, 490 ] ], "normalized": [] }, { "id": "5450", "type": "DNA_domain_or_region", "text": [ "kappa 3" ], "offsets": [ [ 492, 499 ] ], "normalized": [] }, { "id": "5451", "type": "other_name", "text": [ "cyclosporin A-sensitive induction" ], "offsets": [ [ 542, 575 ] ], "normalized": [] }, { "id": "5452", "type": "other_organic_compound", "text": [ "cyclosporin A" ], "offsets": [ [ 542, 555 ] ], "normalized": [] }, { "id": "5453", "type": "DNA_domain_or_region", "text": [ "TNF alpha gene" ], "offsets": [ [ 583, 597 ] ], "normalized": [] }, { "id": "5454", "type": "protein_molecule", "text": [ "TNF" ], "offsets": [ [ 583, 586 ] ], "normalized": [] }, { "id": "5455", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 611, 618 ] ], "normalized": [] }, { "id": "5456", "type": "protein_molecule", "text": [ "kappa 3 binding factor" ], "offsets": [ [ 650, 672 ] ], "normalized": [] }, { "id": "5457", "type": "DNA_domain_or_region", "text": [ "kappa 3" ], "offsets": [ [ 650, 657 ] ], "normalized": [] }, { "id": "5458", "type": "protein_molecule", "text": [ "NFATp" ], "offsets": [ [ 682, 687 ] ], "normalized": [] }, { "id": "5459", "type": "protein_family_or_group", "text": [ "cyclosporin-sensitive DNA-binding protein" ], "offsets": [ [ 691, 732 ] ], "normalized": [] }, { "id": "5460", "type": "other_name", "text": [ "interleukin-2 gene transcription" ], "offsets": [ [ 746, 778 ] ], "normalized": [] }, { "id": "5461", "type": "DNA_domain_or_region", "text": [ "interleukin-2 gene" ], "offsets": [ [ 746, 764 ] ], "normalized": [] }, { "id": "5462", "type": "protein_molecule", "text": [ "NFATp" ], "offsets": [ [ 780, 785 ] ], "normalized": [] }, { "id": "5463", "type": "DNA_domain_or_region", "text": [ "kappa 3 element" ], "offsets": [ [ 816, 831 ] ], "normalized": [] }, { "id": "5464", "type": "DNA_domain_or_region", "text": [ "kappa 3" ], "offsets": [ [ 816, 823 ] ], "normalized": [] }, { "id": "5465", "type": "other_name", "text": [ "TNF alpha gene induction" ], "offsets": [ [ 877, 901 ] ], "normalized": [] }, { "id": "5466", "type": "protein_molecule", "text": [ "TNF" ], "offsets": [ [ 877, 880 ] ], "normalized": [] }, { "id": "5467", "type": "DNA_domain_or_region", "text": [ "kappa 3 element" ], "offsets": [ [ 922, 937 ] ], "normalized": [] }, { "id": "5468", "type": "DNA_domain_or_region", "text": [ "kappa 3" ], "offsets": [ [ 922, 929 ] ], "normalized": [] }, { "id": "5469", "type": "DNA_domain_or_region", "text": [ "NFATp-binding sites" ], "offsets": [ [ 978, 997 ] ], "normalized": [] }, { "id": "5470", "type": "protein_molecule", "text": [ "NFATp" ], "offsets": [ [ 978, 983 ] ], "normalized": [] }, { "id": "5471", "type": "DNA_domain_or_region", "text": [ "cyclosporin-sensitive promoter element" ], "offsets": [ [ 1027, 1065 ] ], "normalized": [] }, { "id": "5472", "type": "DNA_domain_or_region", "text": [ "promoter element" ], "offsets": [ [ 1049, 1065 ] ], "normalized": [] }, { "id": "5473", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 1069, 1076 ] ], "normalized": [] }, { "id": "5474", "type": "protein_molecule", "text": [ "NFATp" ], "offsets": [ [ 1110, 1115 ] ], "normalized": [] }, { "id": "5475", "type": "protein_molecule", "text": [ "NFATp" ], "offsets": [ [ 1136, 1141 ] ], "normalized": [] }, { "id": "5476", "type": "other_name", "text": [ "transcriptional activation" ], "offsets": [ [ 1145, 1171 ] ], "normalized": [] }, { "id": "5477", "type": "protein_molecule", "text": [ "interleukin-2" ], "offsets": [ [ 1184, 1197 ] ], "normalized": [] }, { "id": "5478", "type": "DNA_family_or_group", "text": [ "TNF alpha genes" ], "offsets": [ [ 1202, 1217 ] ], "normalized": [] }, { "id": "5479", "type": "protein_family_or_group", "text": [ "TNF alpha" ], "offsets": [ [ 1202, 1211 ] ], "normalized": [] }, { "id": "5480", "type": "DNA_family_or_group", "text": [ "cytokine genes" ], "offsets": [ [ 1308, 1322 ] ], "normalized": [] }, { "id": "5481", "type": "other_name", "text": [ "T cell activation" ], "offsets": [ [ 1359, 1376 ] ], "normalized": [] } ]

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[ { "id": "5483", "type": "title", "text": [ "Regulation and specificity of MNDA expression in monocytes, macrophages, and leukemia/B lymphoma cell lines." ], "offsets": [ [ 0, 108 ] ] }, { "id": "5484", "type": "abstract", "text": [ "The expression of the human myeloid cell nuclear differentiation antigen (MNDA) was observed specifically in cells of the granulocyte-macrophage lineage in our earlier reports. The specificity of MNDA expression for cells in the granulocyte-macrophage lineage was reexamined in cell lines established from patients with Philadelphia chromosome-positive chronic myeloid leukemia. Cell lines that expressed MNDA exhibited myeloid cell features and granulocyte or monocyte differentiation could be induced in vitro, while cell lines exhibiting properties of very early stage cells or multipotential cells did not express MNDA. Cells originating from cases of Burkitt's lymphoma were negative. By contrast, three lymphoblastoid cell lines (immortalized in vitro with Epstein-Barr virus) were weakly positive and MNDA was up-regulated by interferon-alpha (IFN-alpha) treatment. As we reported previously, MNDA mRNA level in adherent monocytes is elevated by IFN-alpha; in this study, we further assessed MNDA expression in in vitro monocyte-derived macrophages. Three additional agents (endotoxin, phytohemagglutinin, and phorbol ester) and other conditions that affect function, cytokine production, differentiation, and/or growth of monocytes were examined for their ability to alter MNDA expression. The results varied with the agent, cell type, and stage of differentiation. Changes in MNDA expression occurred slowly (hours to days), suggesting that MNDA could mediate changes realized over a long period. The results also reveal a discordance in certain MNDA positive cells between steady-state levels or changes in levels of protein and mRNA indicating that the regulation of MNDA expression occurs at more than one point. Changes in MNDA expression are consistent with a role in opposing macrophage differentiation and activation of monocytes/macrophages." ], "offsets": [ [ 109, 1967 ] ] } ]

[ { "id": "5485", "type": "other_name", "text": [ "MNDA expression" ], "offsets": [ [ 30, 45 ] ], "normalized": [] }, { "id": "5486", "type": "protein_molecule", "text": [ "MNDA" ], "offsets": [ [ 30, 34 ] ], "normalized": [] }, { "id": "5487", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 49, 58 ] ], "normalized": [] }, { "id": "5488", "type": "cell_type", "text": [ "macrophages" ], "offsets": [ [ 60, 71 ] ], "normalized": [] }, { "id": "5489", "type": "cell_line", "text": [ "leukemia/B lymphoma cell lines" ], "offsets": [ [ 77, 107 ] ], "normalized": [] }, { "id": "5490", "type": "protein_molecule", "text": [ "human myeloid cell nuclear differentiation antigen" ], "offsets": [ [ 131, 181 ] ], "normalized": [] }, { "id": "5491", "type": "protein_molecule", "text": [ "MNDA" ], "offsets": [ [ 183, 187 ] ], "normalized": [] }, { "id": "5492", "type": "other_name", "text": [ "granulocyte-macrophage lineage" ], "offsets": [ [ 231, 261 ] ], "normalized": [] }, { "id": "5493", "type": "other_name", "text": [ "MNDA expression" ], "offsets": [ [ 305, 320 ] ], "normalized": [] }, { "id": "5494", "type": "protein_molecule", "text": [ "MNDA" ], "offsets": [ [ 305, 309 ] ], "normalized": [] }, { "id": "5495", "type": "other_name", "text": [ "granulocyte-macrophage lineage" ], "offsets": [ [ 338, 368 ] ], "normalized": [] }, { "id": "5496", "type": "cell_line", "text": [ "cell lines" ], "offsets": [ [ 387, 397 ] ], "normalized": [] }, { "id": "5497", "type": "multi_cell", "text": [ "patients" ], "offsets": [ [ 415, 423 ] ], "normalized": [] }, { "id": "5498", "type": "other_name", "text": [ "Philadelphia chromosome-positive chronic myeloid leukemia" ], "offsets": [ [ 429, 486 ] ], "normalized": [] }, { "id": "5499", "type": "protein_molecule", "text": [ "MNDA" ], "offsets": [ [ 514, 518 ] ], "normalized": [] }, { "id": "5500", "type": "other_name", "text": [ "myeloid cell features" ], "offsets": [ [ 529, 550 ] ], "normalized": [] }, { "id": "5501", "type": "(OR other_name other_name)", "text": [ "granulocyte or monocyte differentiation" ], "offsets": [ [ 555, 594 ] ], "normalized": [] }, { "id": "5502", "type": "", "text": [ "granulocyte" ], "offsets": [ [ 555, 566 ] ], "normalized": [] }, { "id": "5503", "type": "", "text": [ "monocyte" ], "offsets": [ [ 570, 578 ] ], "normalized": [] }, { "id": "5504", "type": "", "text": [ "differentiation" ], "offsets": [ [ 579, 594 ] ], "normalized": [] }, { "id": "5505", "type": "cell_type", "text": [ "multipotential cells" ], "offsets": [ [ 690, 710 ] ], "normalized": [] }, { "id": "5506", "type": "protein_molecule", "text": [ "MNDA" ], "offsets": [ [ 727, 731 ] ], "normalized": [] }, { "id": "5507", "type": "other_name", "text": [ "Burkitt's lymphoma" ], "offsets": [ [ 765, 783 ] ], "normalized": [] }, { "id": "5508", "type": "cell_line", "text": [ "lymphoblastoid cell lines" ], "offsets": [ [ 818, 843 ] ], "normalized": [] }, { "id": "5509", "type": "virus", "text": [ "Epstein-Barr virus" ], "offsets": [ [ 872, 890 ] ], "normalized": [] }, { "id": "5510", "type": "protein_molecule", "text": [ "MNDA" ], "offsets": [ [ 917, 921 ] ], "normalized": [] }, { "id": "5511", "type": "other_name", "text": [ "interferon-alpha (IFN-alpha) treatment" ], "offsets": [ [ 942, 980 ] ], "normalized": [] }, { "id": "5512", "type": "protein_molecule", "text": [ "interferon-alpha" ], "offsets": [ [ 942, 958 ] ], "normalized": [] }, { "id": "5513", "type": "protein_molecule", "text": [ "IFN-alpha" ], "offsets": [ [ 960, 969 ] ], "normalized": [] }, { "id": "5514", "type": "other_name", "text": [ "MNDA mRNA level" ], "offsets": [ [ 1009, 1024 ] ], "normalized": [] }, { "id": "5515", "type": "RNA_molecule", "text": [ "MNDA mRNA" ], "offsets": [ [ 1009, 1018 ] ], "normalized": [] }, { "id": "5516", "type": "protein_molecule", "text": [ "MNDA" ], "offsets": [ [ 1009, 1013 ] ], "normalized": [] }, { "id": "5517", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 1037, 1046 ] ], "normalized": [] }, { "id": "5518", "type": "protein_molecule", "text": [ "IFN-alpha" ], "offsets": [ [ 1062, 1071 ] ], "normalized": [] }, { "id": "5519", "type": "other_name", "text": [ "MNDA expression" ], "offsets": [ [ 1108, 1123 ] ], "normalized": [] }, { "id": "5520", "type": "protein_molecule", "text": [ "MNDA" ], "offsets": [ [ 1108, 1112 ] ], "normalized": [] }, { "id": "5521", "type": "cell_type", "text": [ "macrophages" ], "offsets": [ [ 1153, 1164 ] ], "normalized": [] }, { "id": "5522", "type": "other_organic_compound", "text": [ "endotoxin" ], "offsets": [ [ 1191, 1200 ] ], "normalized": [] }, { "id": "5523", "type": "protein_molecule", "text": [ "phytohemagglutinin" ], "offsets": [ [ 1202, 1220 ] ], "normalized": [] }, { "id": "5524", "type": "other_organic_compound", "text": [ "phorbol ester" ], "offsets": [ [ 1226, 1239 ] ], "normalized": [] }, { "id": "5525", "type": "other_name", "text": [ "cytokine production" ], "offsets": [ [ 1284, 1303 ] ], "normalized": [] }, { "id": "5526", "type": "protein_family_or_group", "text": [ "cytokine" ], "offsets": [ [ 1284, 1292 ] ], "normalized": [] }, { "id": "5527", "type": "other_name", "text": [ "differentiation" ], "offsets": [ [ 1305, 1320 ] ], "normalized": [] }, { "id": "5528", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 1339, 1348 ] ], "normalized": [] }, { "id": "5529", "type": "other_name", "text": [ "MNDA expression" ], "offsets": [ [ 1390, 1405 ] ], "normalized": [] }, { "id": "5530", "type": "protein_molecule", "text": [ "MNDA" ], "offsets": [ [ 1390, 1394 ] ], "normalized": [] }, { "id": "5531", "type": "other_name", "text": [ "differentiation" ], "offsets": [ [ 1466, 1481 ] ], "normalized": [] }, { "id": "5532", "type": "other_name", "text": [ "MNDA expression" ], "offsets": [ [ 1494, 1509 ] ], "normalized": [] }, { "id": "5533", "type": "protein_molecule", "text": [ "MNDA" ], "offsets": [ [ 1494, 1498 ] ], "normalized": [] }, { "id": "5534", "type": "protein_molecule", "text": [ "MNDA" ], "offsets": [ [ 1559, 1563 ] ], "normalized": [] }, { "id": "5535", "type": "cell_line", "text": [ "MNDA positive cells" ], "offsets": [ [ 1664, 1683 ] ], "normalized": [] }, { "id": "5536", "type": "protein_molecule", "text": [ "MNDA" ], "offsets": [ [ 1664, 1668 ] ], "normalized": [] }, { "id": "5537", "type": "RNA_family_or_group", "text": [ "mRNA" ], "offsets": [ [ 1748, 1752 ] ], "normalized": [] }, { "id": "5538", "type": "other_name", "text": [ "MNDA expression" ], "offsets": [ [ 1787, 1802 ] ], "normalized": [] }, { "id": "5539", "type": "protein_molecule", "text": [ "MNDA" ], "offsets": [ [ 1787, 1791 ] ], "normalized": [] }, { "id": "5540", "type": "other_name", "text": [ "MNDA expression" ], "offsets": [ [ 1845, 1860 ] ], "normalized": [] }, { "id": "5541", "type": "protein_molecule", "text": [ "MNDA" ], "offsets": [ [ 1845, 1849 ] ], "normalized": [] }, { "id": "5542", "type": "other_name", "text": [ "macrophage differentiation" ], "offsets": [ [ 1900, 1926 ] ], "normalized": [] }, { "id": "5543", "type": "other_name", "text": [ "differentiation" ], "offsets": [ [ 1911, 1926 ] ], "normalized": [] }, { "id": "5544", "type": "cell_type", "text": [ "monocytes" ], "offsets": [ [ 1945, 1954 ] ], "normalized": [] }, { "id": "5545", "type": "cell_type", "text": [ "/macrophages" ], "offsets": [ [ 1954, 1966 ] ], "normalized": [] } ]

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[ { "id": "5547", "type": "title", "text": [ "DNA-binding studies of the Epstein-Barr virus nuclear antigen 2 (EBNA-2): evidence for complex formation by latent membrane protein gene promoter-binding proteins in EBNA-2-positive cell lines." ], "offsets": [ [ 0, 193 ] ] }, { "id": "5548", "type": "abstract", "text": [ "The Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA-2) protein is essential for the immortalization of human primary B cells by EBV. EBNA-2 trans-activates cellular and viral genes like CD23, c-fgr, latent membrane protein 1 (LMP1) and terminal protein 1 (TP1). Trans-activation of the TP1 promoter and of the BamHI C promoter has already been investigated in detail and appears to be mediated via protein-protein interactions and not by direct binding of EBNA-2 type A (of EBV type 1) to the DNA. EBNA-2 is able to trans-activate the expression of the LMP gene in several cell lines. Various reports have delineated the cis-acting elements of the LMP promoter through which EBNA-2 mediates trans-activation. To determine whether EBNA-2 also trans-activates the LMP promoter by protein-protein interactions, we performed a series of gel retardation assays and competition experiments with LMP promoter fragments of different sizes. We determined that the protein-binding region on the LMP promoter was within a 42 bp fragment encompassing nucleotides -135 to -176 relative to the LMP transcriptional start site. None of the DNA fragments investigated indicated interaction of EBNA-2 with the DNA via protein-protein interactions. No significant differences between EBNA-2-positive and EBNA-2-negative nuclear extracts could be seen in the gel retardation assay under conditions that clearly showed binding of EBNA-2A to the TP1 promoter. However, analysis of sucrose gradient fractions in the gel retardation assay provided evidence that the LMP promoter-binding proteins form a complex of higher M(r) in EBNA-2-positive cell extracts. These complexes were destroyed by detergent. We deduce from these results that EBNA-2-positive cells might indeed contain specific complexes bound to the LMP promoter which are, however, too labile to be detected in a standard gel retardation assay." ], "offsets": [ [ 194, 2080 ] ] } ]

[ { "id": "5549", "type": "protein_molecule", "text": [ "Epstein-Barr virus nuclear antigen 2" ], "offsets": [ [ 27, 63 ] ], "normalized": [] }, { "id": "5550", "type": "virus", "text": [ "Epstein-Barr virus" ], "offsets": [ [ 27, 45 ] ], "normalized": [] }, { "id": "5551", "type": "protein_molecule", "text": [ "EBNA-2" ], "offsets": [ [ 65, 71 ] ], "normalized": [] }, { "id": "5552", "type": "protein_family_or_group", "text": [ "latent membrane protein gene promoter-binding proteins" ], "offsets": [ [ 108, 162 ] ], "normalized": [] }, { "id": "5553", "type": "cell_line", "text": [ "EBNA-2-positive cell lines" ], "offsets": [ [ 166, 192 ] ], "normalized": [] }, { "id": "5554", "type": "protein_molecule", "text": [ "EBNA-2" ], "offsets": [ [ 166, 172 ] ], "normalized": [] }, { "id": "5555", "type": "protein_molecule", "text": [ "Epstein-Barr virus (EBV) nuclear antigen 2" ], "offsets": [ [ 198, 240 ] ], "normalized": [] }, { "id": "5556", "type": "virus", "text": [ "Epstein-Barr virus" ], "offsets": [ [ 198, 216 ] ], "normalized": [] }, { "id": "5557", "type": "virus", "text": [ "EBV" ], "offsets": [ [ 218, 221 ] ], "normalized": [] }, { "id": "5558", "type": "protein_molecule", "text": [ "EBNA-2" ], "offsets": [ [ 242, 248 ] ], "normalized": [] }, { "id": "5559", "type": "cell_type", "text": [ "human primary B cells" ], "offsets": [ [ 298, 319 ] ], "normalized": [] }, { "id": "5560", "type": "virus", "text": [ "EBV" ], "offsets": [ [ 323, 326 ] ], "normalized": [] }, { "id": "5561", "type": "protein_molecule", "text": [ "EBNA-2" ], "offsets": [ [ 328, 334 ] ], "normalized": [] }, { "id": "5562", "type": "(AND DNA_family_or_group DNA_family_or_group)", "text": [ "cellular and viral genes" ], "offsets": [ [ 351, 375 ] ], "normalized": [] }, { "id": "5563", "type": "", "text": [ "cellular" ], "offsets": [ [ 351, 359 ] ], "normalized": [] }, { "id": "5564", "type": "", "text": [ "viral" ], "offsets": [ [ 364, 369 ] ], "normalized": [] }, { "id": "5565", "type": "", "text": [ "genes" ], "offsets": [ [ 370, 375 ] ], "normalized": [] }, { "id": "5566", "type": "DNA_domain_or_region", "text": [ "CD23" ], "offsets": [ [ 381, 385 ] ], "normalized": [] }, { "id": "5567", "type": "DNA_domain_or_region", "text": [ "c-fgr" ], "offsets": [ [ 387, 392 ] ], "normalized": [] }, { "id": "5568", "type": "protein_molecule", "text": [ "latent membrane protein 1" ], "offsets": [ [ 394, 419 ] ], "normalized": [] }, { "id": "5569", "type": "protein_molecule", "text": [ "LMP1" ], "offsets": [ [ 421, 425 ] ], "normalized": [] }, { "id": "5570", "type": "protein_molecule", "text": [ "terminal protein 1" ], "offsets": [ [ 431, 449 ] ], "normalized": [] }, { "id": "5571", "type": "protein_molecule", "text": [ "TP1" ], "offsets": [ [ 451, 454 ] ], "normalized": [] }, { "id": "5572", "type": "DNA_domain_or_region", "text": [ "TP1 promoter" ], "offsets": [ [ 481, 493 ] ], "normalized": [] }, { "id": "5573", "type": "DNA_domain_or_region", "text": [ "BamHI C promoter" ], "offsets": [ [ 505, 521 ] ], "normalized": [] }, { "id": "5574", "type": "other_name", "text": [ "protein-protein interactions" ], "offsets": [ [ 593, 621 ] ], "normalized": [] }, { "id": "5575", "type": "protein_molecule", "text": [ "EBNA-2 type A" ], "offsets": [ [ 651, 664 ] ], "normalized": [] }, { "id": "5576", "type": "protein_molecule", "text": [ "EBNA-2" ], "offsets": [ [ 651, 657 ] ], "normalized": [] }, { "id": "5577", "type": "virus", "text": [ "EBV type 1" ], "offsets": [ [ 669, 679 ] ], "normalized": [] }, { "id": "5578", "type": "protein_molecule", "text": [ "EBNA-2" ], "offsets": [ [ 693, 699 ] ], "normalized": [] }, { "id": "5579", "type": "DNA_domain_or_region", "text": [ "LMP gene" ], "offsets": [ [ 748, 756 ] ], "normalized": [] }, { "id": "5580", "type": "DNA_domain_or_region", "text": [ "cis-acting elements" ], "offsets": [ [ 816, 835 ] ], "normalized": [] }, { "id": "5581", "type": "DNA_domain_or_region", "text": [ "LMP promoter" ], "offsets": [ [ 843, 855 ] ], "normalized": [] }, { "id": "5582", "type": "protein_molecule", "text": [ "EBNA-2" ], "offsets": [ [ 870, 876 ] ], "normalized": [] }, { "id": "5583", "type": "other_name", "text": [ "trans-activation" ], "offsets": [ [ 886, 902 ] ], "normalized": [] }, { "id": "5584", "type": "protein_molecule", "text": [ "EBNA-2" ], "offsets": [ [ 925, 931 ] ], "normalized": [] }, { "id": "5585", "type": "DNA_domain_or_region", "text": [ "LMP promoter" ], "offsets": [ [ 957, 969 ] ], "normalized": [] }, { "id": "5586", "type": "other_name", "text": [ "protein-protein interactions" ], "offsets": [ [ 973, 1001 ] ], "normalized": [] }, { "id": "5587", "type": "other_name", "text": [ "gel retardation assays" ], "offsets": [ [ 1028, 1050 ] ], "normalized": [] }, { "id": "5588", "type": "DNA_molecule", "text": [ "LMP promoter fragments" ], "offsets": [ [ 1084, 1106 ] ], "normalized": [] }, { "id": "5589", "type": "DNA_domain_or_region", "text": [ "LMP promoter" ], "offsets": [ [ 1084, 1096 ] ], "normalized": [] }, { "id": "5590", "type": "DNA_domain_or_region", "text": [ "protein-binding region" ], "offsets": [ [ 1150, 1172 ] ], "normalized": [] }, { "id": "5591", "type": "DNA_domain_or_region", "text": [ "LMP promoter" ], "offsets": [ [ 1180, 1192 ] ], "normalized": [] }, { "id": "5592", "type": "DNA_domain_or_region", "text": [ "42 bp fragment" ], "offsets": [ [ 1206, 1220 ] ], "normalized": [] }, { "id": "5593", "type": "DNA_substructure", "text": [ "nucleotides -135 to -176" ], "offsets": [ [ 1234, 1258 ] ], "normalized": [] }, { "id": "5594", "type": "DNA_domain_or_region", "text": [ "LMP transcriptional start site" ], "offsets": [ [ 1275, 1305 ] ], "normalized": [] }, { "id": "5595", "type": "protein_molecule", "text": [ "EBNA-2" ], "offsets": [ [ 1371, 1377 ] ], "normalized": [] }, { "id": "5596", "type": "other_name", "text": [ "protein-protein interactions" ], "offsets": [ [ 1395, 1423 ] ], "normalized": [] }, { "id": "5597", "type": "protein_molecule", "text": [ "EBNA-2" ], "offsets": [ [ 1460, 1466 ] ], "normalized": [] }, { "id": "5598", "type": "protein_molecule", "text": [ "EBNA-2" ], "offsets": [ [ 1480, 1486 ] ], "normalized": [] }, { "id": "5599", "type": "cell_component", "text": [ "nuclear extracts" ], "offsets": [ [ 1496, 1512 ] ], "normalized": [] }, { "id": "5600", "type": "other_name", "text": [ "gel retardation assay" ], "offsets": [ [ 1534, 1555 ] ], "normalized": [] }, { "id": "5601", "type": "protein_molecule", "text": [ "EBNA-2A" ], "offsets": [ [ 1604, 1611 ] ], "normalized": [] }, { "id": "5602", "type": "DNA_domain_or_region", "text": [ "TP1 promoter" ], "offsets": [ [ 1619, 1631 ] ], "normalized": [] }, { "id": "5603", "type": "other_name", "text": [ "sucrose gradient fractions" ], "offsets": [ [ 1654, 1680 ] ], "normalized": [] }, { "id": "5604", "type": "other_name", "text": [ "gel retardation assay" ], "offsets": [ [ 1688, 1709 ] ], "normalized": [] }, { "id": "5605", "type": "protein_family_or_group", "text": [ "LMP promoter-binding proteins" ], "offsets": [ [ 1737, 1766 ] ], "normalized": [] }, { "id": "5606", "type": "DNA_domain_or_region", "text": [ "LMP promoter" ], "offsets": [ [ 1737, 1749 ] ], "normalized": [] }, { "id": "5607", "type": "other_name", "text": [ "EBNA-2-positive cell extracts" ], "offsets": [ [ 1800, 1829 ] ], "normalized": [] }, { "id": "5608", "type": "cell_type", "text": [ "EBNA-2-positive cell" ], "offsets": [ [ 1800, 1820 ] ], "normalized": [] }, { "id": "5609", "type": "protein_molecule", "text": [ "EBNA-2" ], "offsets": [ [ 1800, 1806 ] ], "normalized": [] }, { "id": "5610", "type": "cell_line", "text": [ "EBNA-2-positive cells" ], "offsets": [ [ 1910, 1931 ] ], "normalized": [] }, { "id": "5611", "type": "protein_molecule", "text": [ "EBNA-2" ], "offsets": [ [ 1910, 1916 ] ], "normalized": [] }, { "id": "5612", "type": "protein_complex", "text": [ "specific complexes" ], "offsets": [ [ 1953, 1971 ] ], "normalized": [] }, { "id": "5613", "type": "DNA_domain_or_region", "text": [ "LMP promoter" ], "offsets": [ [ 1985, 1997 ] ], "normalized": [] }, { "id": "5614", "type": "other_name", "text": [ "gel retardation assay" ], "offsets": [ [ 2058, 2079 ] ], "normalized": [] } ]

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[ { "id": "5616", "type": "title", "text": [ "Simultaneous activation of Ig and Oct-2 synthesis and reduction of surface MHC class II expression by IL-6." ], "offsets": [ [ 0, 107 ] ] }, { "id": "5617", "type": "abstract", "text": [ "Terminal differentiation of B cells to plasma cells in vivo is characterized by secretion of Ig and extinction of MHC class II expression on the cell surface. We show that IL-6 signaling leads to marked increases in the synthesis and secretion of Ig in clonal human B cell lines and newly isolated polyclonal B lymphocytes in vitro. The IL-6-induced cells resemble plasma cells in ultrastructure and in reduced expression of surface MHC class II. Enhanced Ig synthesis is a result of coordinated transcriptional activation of Ig genes without promoter or isotype specificity, and differential accumulation of the mRNA encoding the secreted form of Ig heavy chain. It is saturable and subject to negative control when IL-6 stimulation is prolonged. Coordinate with temporal changes in Ig synthesis, the DNA-binding activity and the synthesis of the B cell-enriched transcription factor Oct-2 are regulated. Thus, differentiation of B cells with IL-6 in vitro recapitulates the hallmarks of terminal B differentiation in vivo; Oct-2 may have a role in this process." ], "offsets": [ [ 108, 1171 ] ] } ]

[ { "id": "5618", "type": "protein_family_or_group", "text": [ "Ig" ], "offsets": [ [ 27, 29 ] ], "normalized": [] }, { "id": "5619", "type": "other_name", "text": [ "Oct-2 synthesis" ], "offsets": [ [ 34, 49 ] ], "normalized": [] }, { "id": "5620", "type": "protein_molecule", "text": [ "Oct-2" ], "offsets": [ [ 34, 39 ] ], "normalized": [] }, { "id": "5621", "type": "other_name", "text": [ "MHC class II expression" ], "offsets": [ [ 75, 98 ] ], "normalized": [] }, { "id": "5622", "type": "protein_family_or_group", "text": [ "MHC class II" ], "offsets": [ [ 75, 87 ] ], "normalized": [] }, { "id": "5623", "type": "protein_molecule", "text": [ "IL-6" ], "offsets": [ [ 102, 106 ] ], "normalized": [] }, { "id": "5624", "type": "cell_type", "text": [ "B cells" ], "offsets": [ [ 136, 143 ] ], "normalized": [] }, { "id": "5625", "type": "cell_type", "text": [ "plasma cells" ], "offsets": [ [ 147, 159 ] ], "normalized": [] }, { "id": "5626", "type": "protein_family_or_group", "text": [ "Ig" ], "offsets": [ [ 201, 203 ] ], "normalized": [] }, { "id": "5627", "type": "other_name", "text": [ "MHC class II expression" ], "offsets": [ [ 222, 245 ] ], "normalized": [] }, { "id": "5628", "type": "protein_family_or_group", "text": [ "MHC class II" ], "offsets": [ [ 222, 234 ] ], "normalized": [] }, { "id": "5629", "type": "protein_molecule", "text": [ "IL-6" ], "offsets": [ [ 280, 284 ] ], "normalized": [] }, { "id": "5630", "type": "protein_family_or_group", "text": [ "Ig" ], "offsets": [ [ 355, 357 ] ], "normalized": [] }, { "id": "5631", "type": "cell_line", "text": [ "clonal human B cell lines" ], "offsets": [ [ 361, 386 ] ], "normalized": [] }, { "id": "5632", "type": "cell_type", "text": [ "isolated polyclonal B lymphocytes" ], "offsets": [ [ 397, 430 ] ], "normalized": [] }, { "id": "5633", "type": "cell_line", "text": [ "IL-6-induced cells" ], "offsets": [ [ 445, 463 ] ], "normalized": [] }, { "id": "5634", "type": "cell_type", "text": [ "plasma cells" ], "offsets": [ [ 473, 485 ] ], "normalized": [] }, { "id": "5635", "type": "protein_family_or_group", "text": [ "surface MHC class II" ], "offsets": [ [ 533, 553 ] ], "normalized": [] }, { "id": "5636", "type": "protein_family_or_group", "text": [ "Ig" ], "offsets": [ [ 564, 566 ] ], "normalized": [] }, { "id": "5637", "type": "DNA_family_or_group", "text": [ "Ig genes" ], "offsets": [ [ 634, 642 ] ], "normalized": [] }, { "id": "5638", "type": "protein_family_or_group", "text": [ "Ig" ], "offsets": [ [ 634, 636 ] ], "normalized": [] }, { "id": "5639", "type": "RNA_family_or_group", "text": [ "mRNA" ], "offsets": [ [ 721, 725 ] ], "normalized": [] }, { "id": "5640", "type": "protein_subunit", "text": [ "Ig heavy chain" ], "offsets": [ [ 756, 770 ] ], "normalized": [] }, { "id": "5641", "type": "protein_family_or_group", "text": [ "Ig" ], "offsets": [ [ 756, 758 ] ], "normalized": [] }, { "id": "5642", "type": "other_name", "text": [ "IL-6 stimulation" ], "offsets": [ [ 825, 841 ] ], "normalized": [] }, { "id": "5643", "type": "protein_molecule", "text": [ "IL-6" ], "offsets": [ [ 825, 829 ] ], "normalized": [] }, { "id": "5644", "type": "other_name", "text": [ "Ig synthesis" ], "offsets": [ [ 892, 904 ] ], "normalized": [] }, { "id": "5645", "type": "protein_family_or_group", "text": [ "Ig" ], "offsets": [ [ 892, 894 ] ], "normalized": [] }, { "id": "5646", "type": "other_name", "text": [ "DNA-binding activity" ], "offsets": [ [ 910, 930 ] ], "normalized": [] }, { "id": "5647", "type": "protein_family_or_group", "text": [ "B cell-enriched transcription factor" ], "offsets": [ [ 956, 992 ] ], "normalized": [] }, { "id": "5648", "type": "protein_molecule", "text": [ "Oct-2" ], "offsets": [ [ 993, 998 ] ], "normalized": [] }, { "id": "5649", "type": "other_name", "text": [ "differentiation" ], "offsets": [ [ 1020, 1035 ] ], "normalized": [] }, { "id": "5650", "type": "cell_type", "text": [ "B cells" ], "offsets": [ [ 1039, 1046 ] ], "normalized": [] }, { "id": "5651", "type": "protein_molecule", "text": [ "IL-6" ], "offsets": [ [ 1052, 1056 ] ], "normalized": [] }, { "id": "5652", "type": "other_name", "text": [ "B differentiation" ], "offsets": [ [ 1106, 1123 ] ], "normalized": [] }, { "id": "5653", "type": "protein_molecule", "text": [ "Oct-2" ], "offsets": [ [ 1133, 1138 ] ], "normalized": [] } ]

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[ { "id": "5655", "type": "title", "text": [ "T-cell functional regions of the human IL-3 proximal promoter." ], "offsets": [ [ 0, 62 ] ] }, { "id": "5656", "type": "abstract", "text": [ "The human interleukin-3 (IL-3) gene is expressed almost exclusively in activated T cells. Its expression is regulated at both the transcriptional and post-transcriptional level. We have previously shown that treatment of Jurkat T cells with phytohemaglutinin (PHA) and the phorbol ester, PMA, activated transcription initiation from the IL-3 gene. To define the regions of the gene required for transcription activation, we generated a series of reporter constructs containing different regions of the IL-3 gene 5' and 3' flanking sequences. Both positive and negative regulatory elements were identified in the proximal 5' flanking region of the IL-3 gene. The promoter region between -173 and -60 contained the strongest activating elements. The transcription factor AP-1 could bind to this positive activator region of the promoter. We also examined the function of the IL-3 CK-1/CK-2 elements that are present in many cytokine genes and found that they acted as a repressor of basal level expression when cloned upstream of a heterologous promoter but were also inducible by PMA/PHA." ], "offsets": [ [ 63, 1150 ] ] } ]

[ { "id": "5657", "type": "DNA_domain_or_region", "text": [ "T-cell functional regions" ], "offsets": [ [ 0, 25 ] ], "normalized": [] }, { "id": "5658", "type": "DNA_domain_or_region", "text": [ "human IL-3 proximal promoter" ], "offsets": [ [ 33, 61 ] ], "normalized": [] }, { "id": "5659", "type": "DNA_domain_or_region", "text": [ "human interleukin-3 (IL-3) gene" ], "offsets": [ [ 67, 98 ] ], "normalized": [] }, { "id": "5660", "type": "protein_molecule", "text": [ "IL-3" ], "offsets": [ [ 88, 92 ] ], "normalized": [] }, { "id": "5661", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 144, 151 ] ], "normalized": [] }, { "id": "5662", "type": "cell_line", "text": [ "Jurkat T cells" ], "offsets": [ [ 284, 298 ] ], "normalized": [] }, { "id": "5663", "type": "cell_type", "text": [ "T cells" ], "offsets": [ [ 291, 298 ] ], "normalized": [] }, { "id": "5664", "type": "protein_molecule", "text": [ "phytohemaglutinin" ], "offsets": [ [ 304, 321 ] ], "normalized": [] }, { "id": "5665", "type": "protein_molecule", "text": [ "PHA" ], "offsets": [ [ 323, 326 ] ], "normalized": [] }, { "id": "5666", "type": "other_organic_compound", "text": [ "phorbol ester" ], "offsets": [ [ 336, 349 ] ], "normalized": [] }, { "id": "5667", "type": "other_organic_compound", "text": [ "PMA" ], "offsets": [ [ 351, 354 ] ], "normalized": [] }, { "id": "5668", "type": "DNA_domain_or_region", "text": [ "IL-3 gene" ], "offsets": [ [ 400, 409 ] ], "normalized": [] }, { "id": "5669", "type": "DNA_domain_or_region", "text": [ "IL-3 gene 5' and 3' flanking sequences" ], "offsets": [ [ 565, 603 ] ], "normalized": [] }, { "id": "5670", "type": "DNA_domain_or_region", "text": [ "IL-3 gene" ], "offsets": [ [ 565, 574 ] ], "normalized": [] }, { "id": "5671", "type": "(AND DNA_family_or_group DNA_family_or_group)", "text": [ "positive and negative regulatory elements" ], "offsets": [ [ 610, 651 ] ], "normalized": [] }, { "id": "5672", "type": "", "text": [ "positive" ], "offsets": [ [ 610, 618 ] ], "normalized": [] }, { "id": "5673", "type": "", "text": [ "negative" ], "offsets": [ [ 623, 631 ] ], "normalized": [] }, { "id": "5674", "type": "", "text": [ "regulatory elements" ], "offsets": [ [ 632, 651 ] ], "normalized": [] }, { "id": "5675", "type": "DNA_domain_or_region", "text": [ "proximal 5' flanking region" ], "offsets": [ [ 675, 702 ] ], "normalized": [] }, { "id": "5676", "type": "DNA_domain_or_region", "text": [ "IL-3 gene" ], "offsets": [ [ 710, 719 ] ], "normalized": [] }, { "id": "5677", "type": "DNA_domain_or_region", "text": [ "promoter region" ], "offsets": [ [ 725, 740 ] ], "normalized": [] }, { "id": "5678", "type": "DNA_domain_or_region", "text": [ "-173 and -60" ], "offsets": [ [ 749, 761 ] ], "normalized": [] }, { "id": "5679", "type": "DNA_domain_or_region", "text": [ "activating elements" ], "offsets": [ [ 786, 805 ] ], "normalized": [] }, { "id": "5680", "type": "protein_family_or_group", "text": [ "transcription factor" ], "offsets": [ [ 811, 831 ] ], "normalized": [] }, { "id": "5681", "type": "protein_molecule", "text": [ "AP-1" ], "offsets": [ [ 832, 836 ] ], "normalized": [] }, { "id": "5682", "type": "DNA_domain_or_region", "text": [ "IL-3 CK-1/CK-2 elements" ], "offsets": [ [ 936, 959 ] ], "normalized": [] }, { "id": "5683", "type": "DNA_family_or_group", "text": [ "cytokine genes" ], "offsets": [ [ 985, 999 ] ], "normalized": [] }, { "id": "5684", "type": "other_name", "text": [ "basal level expression" ], "offsets": [ [ 1044, 1066 ] ], "normalized": [] }, { "id": "5685", "type": "DNA_domain_or_region", "text": [ "heterologous promoter" ], "offsets": [ [ 1093, 1114 ] ], "normalized": [] }, { "id": "5686", "type": "other_organic_compound", "text": [ "PMA" ], "offsets": [ [ 1142, 1145 ] ], "normalized": [] }, { "id": "5687", "type": "protein_molecule", "text": [ "/PHA" ], "offsets": [ [ 1145, 1149 ] ], "normalized": [] } ]

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