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FEBS Lett. 2002 Oct 9;529(2-3):249-55.

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

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Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Campus Universidad Autónoma, 28049 Madrid, Spain.


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.

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