Regulation of mammalian target of rapamycin complex 1 by Bcl-2 and Bcl-XL proteins.
Mammalian target of rapamycin complex 1 (mTORC1) is a key regulator of cell growth and metabolism. Its activity is controlled by various types of signals, including growth factors, nutrients, and stresses. In this study, we show that changes in expression levels of two antiapoptotic proteins, Bcl-2 and Bcl-XL, also affect mTORC1 signaling activity. In cells overexpressing Bcl-XL, mTORC1 activity is increased and becomes less sensitive to growth factor or nutrient conditions. In contrast, reduction in expression levels of the two antiapoptotic proteins inhibits mTORC1 signaling activity. Our results suggest that the effect of Bcl-2 and Bcl-XL on mTORC1 is mediated by FKBP38, an inhibitor of mTORC1. The two proteins compete with mTORC1 for FKBP38 binding and hence alter mTORC1 activity. This study reveals a novel cross-talk between Bcl-2/XL and mTORC1 signaling, which is likely to contribute to cancer development.
['Zou|Huafei|H|', 'Lai|Yumei|Y|', 'Zhao|Xuwen|X|', 'Yan|Gonghong|G|', 'Ma|Dongzhu|D|', 'Cardenes|Nayra|N|', 'Shiva|Sruti|S|', 'Liu|Yongjian|Y|', 'Bai|Xiaochun|X|', 'Jiang|Yong|Y|', 'Jiang|Yu|Y|']
D017209:Apoptosis D015536:Down-Regulation D055785:Gene Knockdown Techniques D045325:HCT116 Cells D057809:HEK293 Cells D006367:HeLa Cells D006801:Humans D000076222:Mechanistic Target of Rapamycin Complex 1 D008928:Mitochondria D046912:Multiprotein Complexes D064549:Myeloid Cell Leukemia Sequence 1 Protein D011485:Protein Binding D021381:Protein Transport D058570:TOR Serine-Threonine Kinases D022021:Tacrolimus Binding Proteins D051020:bcl-X Protein
Bcl-2 Bcl-XL mTORC1 Signaling FKBP38 Mitochondria S6 Kinase mTOR Complex (mTORC)