DIABLO promotes apoptosis by removing MIHA/XIAP from processed caspase 9

被引:155
作者
Ekert, PG
Silke, J
Hawkins, CJ
Verhagen, AM
Vaux, DL [1 ]
机构
[1] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia
[2] Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia
[3] Royal Childrens Hosp, Dept Haematol & Oncol, Parkville, Vic 3052, Australia
基金
英国医学研究理事会;
关键词
apoptosis; IAPs; DIABLO; caspases; BIR;
D O I
10.1083/jcb.152.3.483
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
MIHA is an inhibitor of apoptosis protein (IAP) that can inhibit cell death by direct interaction with caspases, the effector proteases of apoptosis. DIABLO is a mammalian protein that can bind to IAPs and antagonize their antiapoptotic effect, a function analogous to that of the proapoptotic Drosophila molecules, Grim, Reaper, and HID. Here. we show that after UV radiation, MIHA prevented apoptosis by inhibiting caspase 9 and caspase 3 activation. Unlike Bcl-2, MIHA functioned after release of cytochrome c and DIABLO from the mitochondria and was able to bind to both processed caspase 9 and processed caspase 3 to prevent feedback activation of their zymogen forms. Once released into the cytosol, DIABLO bound to MIHA and disrupted its association with processed caspase 9, thereby allowing caspase 9 to activate caspase 3, resulting in apoptosis.
引用
收藏
页码:483 / 490
页数:8
相关论文
共 40 条
[1]   Drosophila grim induces apoptosis in mammalian cells [J].
Clavería, C ;
Albar, JP ;
Serrano, A ;
Buesa, JM ;
Barbero, JL ;
Martínez-A, C ;
Torres, M .
EMBO JOURNAL, 1998, 17 (24) :7199-7208
[2]   CONTROL OF PROGRAMMED CELL-DEATH BY THE BACULOVIRUS GENES P35 AND IAP [J].
CLEM, RJ ;
MILLER, LK .
MOLECULAR AND CELLULAR BIOLOGY, 1994, 14 (08) :5212-5222
[3]  
COGHLAN VM, 1994, J BIOL CHEM, V269, P7658
[4]   AN APOPTOSIS-INHIBITING BACULOVIRUS GENE WITH A ZINC FINGER-LIKE MOTIF [J].
CROOK, NE ;
CLEM, RJ ;
MILLER, LK .
JOURNAL OF VIROLOGY, 1993, 67 (04) :2168-2174
[5]   Solution structure and mutagenesis of the caspase recruitment domain (CARD) from Apaf-1 [J].
Day, CL ;
Dupont, C ;
Lackmann, M ;
Vaux, DL ;
Hinds, MG .
CELL DEATH AND DIFFERENTIATION, 1999, 6 (11) :1125-1132
[6]   X-linked IAP is a direct inhibitor of cell-death proteases [J].
Deveraux, QL ;
Takahashi, R ;
Salvesen, GS ;
Reed, JC .
NATURE, 1997, 388 (6639) :300-304
[7]   Cleavage of human inhibitor of apoptosis protein XIAP results in fragments with distinct specificities for caspases [J].
Deveraux, QL ;
Leo, E ;
Stennicke, HR ;
Welsh, K ;
Salvesen, GS ;
Reed, JC .
EMBO JOURNAL, 1999, 18 (19) :5242-5251
[8]   IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases [J].
Deveraux, QL ;
Roy, N ;
Stennicke, HR ;
Van Arsdale, T ;
Zhou, Q ;
Srinivasula, SM ;
Alnemri, ES ;
Salvesen, GS ;
Reed, JC .
EMBO JOURNAL, 1998, 17 (08) :2215-2223
[9]   Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition [J].
Du, CY ;
Fang, M ;
Li, YC ;
Li, L ;
Wang, XD .
CELL, 2000, 102 (01) :33-42
[10]   A conserved family of cellular genes related to the baculovirus iap gene and encoding apoptosis inhibitors [J].
Duckett, CS ;
Nava, VE ;
Gedrich, RW ;
Clem, RJ ;
VanDongen, JL ;
Gilfillan, MC ;
Shiels, H ;
Hardwick, JM ;
Thompson, CB .
EMBO JOURNAL, 1996, 15 (11) :2685-2694