| First Author | Marsden VS | Year | 2004 |
| Journal | J Cell Biol | Volume | 165 |
| Issue | 6 | Pages | 775-80 |
| PubMed ID | 15210727 | Mgi Jnum | J:91156 |
| Mgi Id | MGI:3046031 | Doi | 10.1083/jcb.200312030 |
| Citation | Marsden VS, et al. (2004) Bcl-2-regulated apoptosis and cytochrome c release can occur independently of both caspase-2 and caspase-9. J Cell Biol 165(6):775-80 |
| abstractText | 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 hematopoietic development. Furthermore, lymphocytes and fibroblasts lacking both remained sensitive to diverse apoptotic stimuli. Dying caspase-2(-/-)9(-/-) lymphocytes displayed multiple hallmarks of caspase-dependent apoptosis, including the release of cytochrome c from mitochondria, and their demise was antagonized by several caspase inhibitors. These findings suggest that caspases other than caspases 2 and 9 can promote cytochrome c release and initiate Bcl-2-regulated apoptosis. |
