Apoptosis initiated by Bcl-2-regulated caspase activation independently of the cytochrome c/Apaf-1/caspase-9 apoptosome
- Author(s)
- Marsden, VS; O'Connor, L; O'Reilly, LA; Silke, J; Metcalf, D; Ekert, PG; Huang, DCS; Cecconi, F; Kuida, K; Tomaselli, KJ; Roy, S; Nicholson, DW; Vaux, DL; Bouillet, P; Adams, JM; Strasser, A;
- Details
- Publication Year 2002-10-10,Volume 419,Issue #6907,Page 634-637
- Journal Title
- NATURE
- Publication Type
- Journal Article
- Abstract
- Apoptosis is an evolutionarily conserved cell suicide process executed by cysteine proteases (caspases) and regulated by the opposing factions of the Bcl-2 protein family(1,2). Mammalian caspase-9 and its activator Apaf-1 were thought to be essential, because mice lacking either of them display neuronal hyperplasia and their lymphocytes and fibroblasts seem resistant to certain apoptotic stimuli(3-6). Because Apaf-1 requires cytochrome c to activate caspase-9, and Bcl-2 prevents mitochondrial cytochrome c release, Bcl-2 is widely believed to inhibit apoptosis by safeguarding mitochondrial membrane integrity(7-9). Our results suggest a different, broader role, because Bcl-2 overexpression increased lymphocyte numbers in mice and inhibited many apoptotic stimuli, but the absence of Apaf-1 or caspase-9 did not. Caspase activity was still discernible in cells lacking Apaf-1 or caspase-9, and a potent caspase antagonist both inhibited apoptosis and retarded cytochrome c release. We conclude that Bcl-2 regulates a caspase activation programme independently of the cytochrome c/Apaf-1/caspase-9 'apoptosome', which seems to amplify rather than initiate the caspase cascade.
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- PROGRAMMED CELL-DEATH; BCL-2; MITOCHONDRIA; PATHWAYS; PROTEASE; MICE; DISTINCT; APAF1; DNA
- Publisher's Version
- https://doi.org/10.1038/nature01101
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2002-10-10 12:00:00