Bcl-2-regulated apoptosis and cytochrome c release can occur independently of both caspase-2 and caspase-9

Abstract

Apoptosis in response to developmental cues and stress stimuli is mediated by caspases that are regulated by the Bcl-2 protein family. Although caspases 2 and 9 have each been proposed as the apical caspase in that pathway, neither is indispensable for the apoptosis of leukocytes or fibroblasts. To investigate whether these caspases share a redundant role in apoptosis initiation, we generated caspase-2-/-9-/- mice. Their overt phenotype, embryonic brain malformation and perinatal lethality mirrored that of caspase-9-/- mice but were not exacerbated. Analysis of adult mice reconstituted with caspase-2-/-9-/- hematopoietic cells revealed that the absence of both caspases did not influence hema..