Proteolytic Processing of the Caspase-9 Zymogen Is Required for   Apoptosome-mediated Activation of Caspase-9

doi:10.1074/jbc.M112.441568

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	Proteolytic Processing of the Caspase-9 Zymogen Is Required for Apoptosome-mediated Activation of Caspase-9
	Hu, Qi ; Wu, Di ; Chen, Wen ; Yan, Zhen ; Shi, Yigong
刊名	journal of biological chemistry
	2013
关键词	CELL-DEATH CYTOCHROME-C INHIBITION XIAP PROCASPASE-9 SMAC/DIABLO MECHANISMS INSIGHTS APAF-1
DOI	10.1074/jbc.M112.441568
英文摘要	Maturation of the single-chain caspase-9 zymogen through autoproteolytic processing is mediated by the Apaf-1 apoptosome at the onset of apoptosis. Processed caspase-9 and the apoptosome form a holoenzyme with robust proteolytic activity that is 2-3 orders of magnitude higher than that of free processed caspase-9. An unresolved important question is the role of caspase-9 processing, with some experimental data suggesting its dispensability. In this study, we demonstrate that, in contrast to wild-type caspase-9, the unprocessed single-chain caspase-9 triple mutant E306A/D315A/D330A (Casp9-TM) could no longer be adequately activated by the apoptosome. Compared with the protease activity of wild-type caspase-9, that of Casp9-TM in the presence of the apoptosome was drastically reduced. The crippled protease activity of Casp9-TM in the presence of the apoptosome is likely attributable to a markedly reduced ability of Casp9-TM to form homodimers. These data identify an essential role for the autoproteolytic processing of caspase-9 in its activation.; Biochemistry & Molecular Biology; SCI(E); EI; 9; ARTICLE; 21; 15142-15147; 288
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/391576]
专题	生命科学学院
推荐引用方式 GB/T 7714	Hu, Qi,Wu, Di,Chen, Wen,et al. Proteolytic Processing of the Caspase-9 Zymogen Is Required for Apoptosome-mediated Activation of Caspase-9[J]. journal of biological chemistry,2013.
APA	Hu, Qi,Wu, Di,Chen, Wen,Yan, Zhen,&Shi, Yigong.(2013).Proteolytic Processing of the Caspase-9 Zymogen Is Required for Apoptosome-mediated Activation of Caspase-9.journal of biological chemistry.
MLA	Hu, Qi,et al."Proteolytic Processing of the Caspase-9 Zymogen Is Required for Apoptosome-mediated Activation of Caspase-9".journal of biological chemistry (2013).