Mcl-1 interacts with truncated bid and inhibits its induction of cytochrome c release and its role in receptor-mediated apoptosis

被引:154
作者
Clohessy, JG
Zhuang, JG
de Boer, J
Gil-Gómez, G
Brady, HJM
机构
[1] Inst Child Hlth, Mol Haematol & Canc Biol Unit, London WC1N 1EH, England
[2] UCL, Great Ormond St Hosp Children, London WC1N 1EH, England
[3] Univ Pompeu Fabra, Inst Municipal Invest Med, Unitat Biol Cellular & Mol, E-03003 Barcelona, Spain
关键词
D O I
10.1074/jbc.M505688200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Engagement of death receptors such as tumor necrosis factor-R1 and Fas brings about the cleavage of cytosolic Bid to truncated Bid (tBid), which translocates to mitochondria to activate Bax/Bak, resulting in the release of cytochrome c. The mechanism underlying the activation, however, is not fully understood. Here, we have identified the anti-apoptotic Bcl-2 family member Mcl-1 as a potent tBid-binding partner. Site-directed mutagenesis reveals that the Bcl-2 homology (BH) 3 domain of tBid is essential for binding to Mcl-1, whereas all threeBHdomains (BH1, BH2, and BH3) of Mcl-1 are required for interaction with tBid. In vitro studies using isolated mitochondria and recombinant proteins demonstrate that Mcl-1 strongly inhibits tBid-induced cytochrome c release. In addition to its ability to interact directly with Bax and Bak, tBid also binds Mcl-1 and displaces Bak from the Mcl-1-Bak complex. Importantly, overexpression of Mcl-1 confers resistance to the induction of apoptosis by both TRAIL and tumor necrosis factor-alpha in HeLa cells, whereas targeting Mcl-1 by RNA interference sensitizes HeLa cells to TRAIL-induced apoptosis. Therefore, our study demonstrates a novel regulation of tBid by Mcl-1 through protein-protein interaction in apoptotic signaling from death receptors to mitochondria.
引用
收藏
页码:5750 / 5759
页数:10
相关论文
共 46 条
[21]   Mitochondrial p53 activates Bak and causes disruption of a Bak-Mcl1 complex [J].
Leu, JIJ ;
Dumont, P ;
Hafey, M ;
Murphy, ME ;
George, DL .
NATURE CELL BIOLOGY, 2004, 6 (05) :443-450
[22]   Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis [J].
Li, HL ;
Zhu, H ;
Xu, CJ ;
Yuan, JY .
CELL, 1998, 94 (04) :491-501
[23]   Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors [J].
Luo, X ;
Budihardjo, I ;
Zou, H ;
Slaughter, C ;
Wang, XD .
CELL, 1998, 94 (04) :481-490
[24]   Control of apoptosis in the immune system: Bcl-2, BH3-only proteins and more [J].
Marsden, VS ;
Strasser, A .
ANNUAL REVIEW OF IMMUNOLOGY, 2003, 21 :71-105
[25]   Fas ligand-induced apoptosis [J].
Nagata, S .
ANNUAL REVIEW OF GENETICS, 1999, 33 :29-55
[26]   Elimination of Mcl-1 is required for the initiation of apoptosis following ultraviolet irradiation [J].
Nijhawan, D ;
Fang, M ;
Traer, E ;
Zhong, Q ;
Gao, WH ;
Du, FH ;
Wang, XD .
GENES & DEVELOPMENT, 2003, 17 (12) :1475-1486
[27]   Up-regulated expression of murine Mc11/EAT, a Bcl-2 related gene, in the early stage of differentiation of murine embryonal carcinoma cells and embryonic stem cells [J].
Okita, H ;
Umezawa, A ;
Suzuki, A ;
Hata, J .
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION, 1998, 1398 (03) :335-341
[28]   Development and maintenance of B and T lymphocytes requires antiapoptotic MCL-1 [J].
Opferman, JT ;
Letai, A ;
Beard, C ;
Sorcinelli, MD ;
Ong, CC ;
Korsmeyer, SJ .
NATURE, 2003, 426 (6967) :671-676
[29]   TNF-α signals apoptosis through a bid-dependent conformational change in Bax that is inhibited by E1B 19K [J].
Perez, D ;
White, E .
MOLECULAR CELL, 2000, 6 (01) :53-63
[30]  
Rinkenberger JL, 2000, GENE DEV, V14, P23