Bcl-xL does not inhibit the function of Apaf-1

被引:68
作者
Newmeyer, DD [1 ]
Bossy-Wetzel, E [1 ]
Kluck, RM [1 ]
Wolf, BB [1 ]
Beere, HM [1 ]
Green, DR [1 ]
机构
[1] La Jolla Inst Allergy & Immunol, San Diego, CA 92121 USA
关键词
Bcl-x(L); apoptosome; Apaf-1; Bcl-2; caspases;
D O I
10.1038/sj.cdd.4400665
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
Bcl-2 and its relative, Bcl-x(L), inhibit apoptotic cell death primarily by controlling the activation of caspase proteases, previous reports have suggested at least two distinct mechanisms: Bcl-2 and Bcl-x(L) may inhibit either the formation of the cytochrome c/Apaf-1/caspase-9 apoptosome complex (by preventing cytochrome c release from mitochondria) or the function of this apoptosome (through a direct interaction of Bcl-2 or Bcl-x(L) with Apaf-1). To evaluate this latter possibility, we added recombinant Bcl-x(L) protein to cell-free apoptotic systems derived from jurkat cells and Xenopus eggs. At low concentrations(50 nM), Bcl-x(L) was able to block the release of cytochrome c from mitochondria, However, although Bcl-x(L) did associate with Apaf-1, it was unable to inhibit caspase activation induced by the addition of cytochrome c, even at much higher concentrations (1-5 mu M), These observations, together with previous results obtained with Bcl-2, argue that Bcl-x(L) and Bcl-2 cannot block the apoptosome-mediated activation of caspase-9.
引用
收藏
页码:402 / 407
页数:6
相关论文
共 44 条
[11]  
Horvitz HR, 1999, CANCER RES, V59, p1701S
[12]   Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation [J].
Hu, YM ;
Benedict, MA ;
Wu, DY ;
Inohara, N ;
Núñez, G .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (08) :4386-4391
[13]   CED-4 induces chromatin condensation in Schizosaccharomyces pombe and is inhibited by direct physical association with CED-9 [J].
James, C ;
Gschmeissner, S ;
Fraser, A ;
Evan, GI .
CURRENT BIOLOGY, 1997, 7 (04) :246-252
[14]   The release of cytochrome c from mitochondria: A primary site for Bcl-2 regulation of apoptosis [J].
Kluck, RM ;
BossyWetzel, E ;
Green, DR ;
Newmeyer, DD .
SCIENCE, 1997, 275 (5303) :1132-1136
[15]   Cytochrome c activation of CPP32-like proteolysis plays a critical role in a Xenopus cell-free apoptosis system [J].
Kluck, RM ;
Martin, SJ ;
Hoffman, BM ;
Zhou, JS ;
Green, DR ;
Newmeyer, DD .
EMBO JOURNAL, 1997, 16 (15) :4639-4649
[16]   Cell-specific induction of apoptosis by microinjection of cytochrome c - Bcl-x(L) has activity independent of cytochrome c release [J].
Li, F ;
Srinivasan, A ;
Wang, Y ;
Armstrong, RC ;
Tomaselli, KJ ;
Fritz, LC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (48) :30299-30305
[17]   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
[18]   Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade [J].
Li, P ;
Nijhawan, D ;
Budihardjo, I ;
Srinivasula, SM ;
Ahmad, M ;
Alnemri, ES ;
Wang, XD .
CELL, 1997, 91 (04) :479-489
[19]   DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger DNA fragmentation during apoptosis [J].
Liu, XS ;
Zou, H ;
Slaughter, C ;
Wang, XD .
CELL, 1997, 89 (02) :175-184
[20]   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