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Apoptosis initiated by Bcl-2-regulated caspase activation independently of the cytochrome c/Apaf-1/caspase-9 apoptosome.
- Source :
-
Nature [Nature] 2002 Oct 10; Vol. 419 (6907), pp. 634-7. Date of Electronic Publication: 2002 Sep 25. - Publication Year :
- 2002
-
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. 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. 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. 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.
- Subjects :
- Animals
Apoptotic Protease-Activating Factor 1
B-Lymphocytes cytology
Caspase 9
Cells, Cultured
Enzyme Activation
Hematopoiesis physiology
Mice
Mice, Inbred C57BL
T-Lymphocytes cytology
Apoptosis
Caspases metabolism
Cytochrome c Group metabolism
Proteins metabolism
Proto-Oncogene Proteins c-bcl-2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0028-0836
- Volume :
- 419
- Issue :
- 6907
- Database :
- MEDLINE
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 12374983
- Full Text :
- https://doi.org/10.1038/nature01101