Human MageB2 Protein Expression Enhances E2F Transcriptional Activity, Cell Proliferation, and Resistance to Ribotoxic Stress.
MageB2 belongs to the melanoma antigen gene (MAGE-I) family of tumor-specific antigens. Expression of this gene has been detected in human tumors of different origins. However, little is known about the protein function and how its expression affects tumor cell phenotypes. In this work, we found that human MageB2 protein promotes tumor cell proliferation in a p53-independent fashion, as observed both in cultured cells and growing tumors in mice. Gene expression analysis showed that MageB2 enhances the activity of E2F transcription factors. Mechanistically, the activation of E2Fs is related to the ability of MageB2 to interact with the E2F inhibitor HDAC1. Cellular distribution of MageB2 protein includes the nucleoli. Nevertheless, ribotoxic drugs rapidly promote its nucleolar exit. We show that MageB2 counteracts E2F inhibition by ribosomal proteins independently of Mdm2 expression. Importantly, MageB2 plays a critical role in impairing cell cycle arrest in response to Actinomycin D. The data presented here support a relevant function for human MageB2 in cancer cells both under cycling and stressed conditions, presenting a distinct functional feature with respect to other characterized MAGE-I proteins.
['Peche|Leticia Y|LY|', 'Ladelfa|María F|MF|', 'Toledo|María F|MF|', 'Mano|Miguel|M|', 'Laiseca|Julieta E|JE|', 'Schneider|Claudio|C|', 'Monte|Martín|M|']
D000818:Animals D000951:Antigens, Neoplasm D000970:Antineoplastic Agents D002453:Cell Cycle D002466:Cell Nucleolus D049109:Cell Proliferation D003609:Dactinomycin D050684:E2F Transcription Factors D005347:Fibroblasts D005786:Gene Expression Regulation D049452:Green Fluorescent Proteins D045325:HCT116 Cells D057809:HEK293 Cells D056284:Histone Deacetylase 1 D006655:Histone Deacetylases D006801:Humans D008546:Melanoma, Experimental D051379:Mice D008810:Mice, Inbred C57BL D009363:Neoplasm Proteins D051736:Proto-Oncogene Proteins c-mdm2 D012270:Ribosomes
cell proliferation E2F transcription factor cancer biology histone deacetylase 1 (HDAC1) molecular cell biology