title: Regulation of mammalian target of rapamycin complex 1 by Bcl-2 and Bcl-XL proteins.
abstract: 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.
authors: From the Department of Pharmacology and Chemical Biology and.
authors: Huafei
authors: H
authors: Zou
authors: Yumei
authors: Y
authors: Lai
authors: Xuwen
authors: X
authors: Zhao
authors: Gonghong
authors: G
authors: Yan
authors: Dongzhu
authors: D
authors: Ma
authors: Nayra
authors: N
authors: Cardenes
authors: Sruti
authors: S
authors: Shiva
authors: Yongjian
authors: Y
authors: Liu
authors: Xiaochun
authors: X
authors: Bai
authors: Yong
authors: Y
authors: Jiang
authors: Yu
authors: Y
authors: Jiang
mesh_terms: 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 / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism*; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D022021:Tacrolimus Binding Proteins / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism*
chemical_list: C471205:FKBP8 protein, human; C579095:MCL1 protein, human; D046912:Multiprotein Complexes; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D051020:bcl-X Protein; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D022021:Tacrolimus Binding Proteins
keywords: Bcl-2; Bcl-XL; FKBP38; Mitochondria; S6 Kinase; Signaling; mTOR Complex (mTORC); mTORC1
references: J Biol Chem. 2001 Nov 23;276(47):44117-28
references: 11546793
references: Cell. 2012 Apr 13;149(2):274-93
references: 22500797
references: J Biol Chem. 1998 Jul 10;273(28):17926-32
references: 9651399
references: FEBS Lett. 2005 Feb 28;579(6):1469-76
references: 15733859
references: Nat Rev Mol Cell Biol. 2008 Jan;9(1):47-59
references: 18097445
references: Nat Cell Biol. 2003 Jan;5(1):28-37
references: 12510191
references: Prostate. 2009 Apr 1;69(5):459-70
references: 19107861
references: Science. 2007 Nov 9;318(5852):977-80
references: 17991864
references: J Biol Chem. 2010 Mar 19;285(12):8621-7
references: 20048149
references: BMC Cancer. 2006 Aug 23;6:213
references: 16928273
references: J Biol Chem. 2004 Aug 13;279(33):34227-39
references: 15175350
references: Cell Cycle. 2011 Jul 15;10(14):2305-16
references: 21670596
references: Nat Rev Mol Cell Biol. 2009 May;10(5):307-18
references: 19339977
references: Cell. 2011 Mar 4;144(5):646-74
references: 21376230
references: Genes Dev. 2003 Apr 1;17(7):832-7
references: 12670866
references: Cell Mol Life Sci. 2010 Jan;67(2):239-53
references: 19823764
references: Cell Death Differ. 2011 Sep;18(9):1414-24
references: 21415859
references: Cancer Res. 2008 May 1;68(9):3421-8
references: 18451170
references: J Biol Chem. 2005 Feb 4;280(5):3483-92
references: 15611130
references: Science. 2000 Nov 3;290(5493):989-92
references: 11062132