Caspase 9 activation by the dsRNA-dependent protein kinase, PKR: molecular mechanism and relevance

被引:49
作者
Gil, J [1 ]
Garcia, MA [1 ]
Esteban, M [1 ]
机构
[1] CSIC, Ctr Nacl Biotecnol, Dept Mol & Cellular Biol, Madrid 28049, Spain
关键词
apoptosis; double-stranded RNA-dependent protein kinase; caspase; 9; cytochrome c; mitochondria;
D O I
10.1016/S0014-5793(02)03348-3
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
The double-stranded RNA-dependent protein kinase (PKR) induces apoptosis by activation of the FADD/caspase 8 pathway. Here we show that upon PKR expression, caspase 9 is processed and activated, correlating with the translocation of cytochrome c to the cytoplasm and breakdown of mitochondrial potential upon Bax insertion. However, treatment of cells with an inhibitor of caspase 9 could not prevent PKR-induced apoptosis. During PKR-induced apoptosis, caspase 9 is activated downstream of caspase 8. Our findings revealed that caspase 9, although dispensable, is a mediator of PKR-induced cell death. (C) 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.
引用
收藏
页码:249 / 255
页数:7
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