Caspase-9 plays a marginal role in serum starvation-induced apoptosis.
Serum withdrawal represents a potent trigger to induce caspase-dependent apoptosis in a series of cell culture models. In rat 423-cells, caspase-8 and caspase-3 were apparently sufficient to initiate and proceed apoptosis without involving the intrinsic amplification loop via caspase-9. To assess the reasons for this inactivity of an otherwise crucial initiator caspase, we examined the ability for apoptosome assembly in 423-cells. Caspase-9 and Apaf-1 were expressed and cytochrome c released from mitochondria upon serum withdrawal. Although functional apoptosomes were assembled successfully in vitro, caspase-9 processing was found essentially refrained during apoptosis in 423-cells. Cell fractionation experiments revealed that sequestration of caspase-9 to cytoskeletal structures in 423-cells contributed to the observed impairment of apoptosome formation. Altogether, these findings provide evidence that serum starvation-induced apoptosis may occur independently of the intrinsic pathway and that caspase-9 sequestration potentially represents a novel biological antiapoptotic strategy.
Schamberger
Chantal J
CJ
Institute of Cancer Research, Medical University of Vienna, 1090 Vienna, Austria. chantal.schamberger@meduniwien.ac.at
Gerner
Christopher
C
Cerni
Christa
C
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053477:Apoptotic Protease-Activating Factor 1; D001798:Blood Proteins / Q000378:metabolism*; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism; D007633:Keratins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000502:physiology
C506592:APAF1 protein, human; C506594:Apaf1 protein, rat; D053477:Apoptotic Protease-Activating Factor 1; D001798:Blood Proteins; D016895:Culture Media, Serum-Free; D006133:Growth Substances; D011506:Proteins; D007633:Keratins; D045304:Cytochromes c; C506433:CASP9 protein, human; C506435:Casp9 protein, rat; D053453:Caspase 9; D020169:Caspases