Caspase 9 activation by the dsRNA-dependent protein kinase, PKR: molecular mechanism and relevance.
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.
Gil
Jesús
J
Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Campus Universidad Autónoma, 28049 Madrid, Spain.
García
Maria Angel
MA
Esteban
Mariano
M
D017209:Apoptosis / Q000502:physiology; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003574:Cytochrome c Group / Q000378:metabolism; D003593:Cytoplasm / Q000201:enzymology; D004789:Enzyme Activation; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000201:enzymology / Q000502:physiology; D019892:eIF-2 Kinase / Q000378:metabolism* / Q000502:physiology
D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D003574:Cytochrome c Group; D019892:eIF-2 Kinase; C506433:CASP9 protein, human; D053453:Caspase 9; D020169:Caspases