| First Author | Potts PR | Year | 2003 |
| Journal | J Cell Biol | Volume | 163 |
| Issue | 4 | Pages | 789-99 |
| PubMed ID | 14623868 | Mgi Jnum | J:86711 |
| Mgi Id | MGI:2681362 | Doi | 10.1083/jcb.200307130 |
| Citation | Potts PR, et al. (2003) Critical function of endogenous XIAP in regulating caspase activation during sympathetic neuronal apoptosis. J Cell Biol 163(4):789-99 |
| abstractText | In sympathetic neurons, unlike most nonneuronal cells, growth factor withdrawal-induced apoptosis requires the development of competence in addition to cytochrome c release to activate caspases. Thus, although most nonneuronal cells die rapidly with cytosolic cytochrome c alone, sympathetic neurons are remarkably resistant unless they develop competence. We have identified endogenous X-linked inhibitor of apoptosis protein (XIAP) as the essential postcytochrome c regulator of caspase activation in these neurons. In contrast to wild-type neurons that are resistant to injection of cytochrome c, XIAP-deficient neurons died rapidly with cytosolic cytochrome c alone. Surprisingly, the release of endogenous Smac was not sufficient to overcome the XIAP resistance in sympathetic neurons. In contrast, the neuronal competence pathway permitted cytochrome c to activate caspases by inducing a marked reduction in XIAP levels in these neurons. Thus, the removal of XIAP inhibition appears both necessary and sufficient for cytochrome c to activate caspases in sympathetic neurons. These data identify a critical function of endogenous XIAP in regulating apoptosis in mammalian cells. |
