Apocytochrome c blocks caspase-9 activation and Bax-induced apoptosis - PubMed (original) (raw)
. 2002 Dec 27;277(52):50834-41.
doi: 10.1074/jbc.M209369200. Epub 2002 Oct 18.
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- PMID: 12393884
- DOI: 10.1074/jbc.M209369200
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Apocytochrome c blocks caspase-9 activation and Bax-induced apoptosis
Angel G Martin et al. J Biol Chem. 2002.
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Abstract
Complex networks of signaling pathways control the apoptotic response and, therefore, cell survival. However, these networks converge on a common machinery, of which the caspase cysteine proteases are key components. Diverse apoptotic stimuli release holocytochrome c from mitochondria, allowing holocytochrome c to bind apoptotic protease activating factor-1 (Apaf-1), which in turn binds caspase-9 both activating this caspase and forming an Apaf-1/caspase-9 holoenzyme. Cytochrome c lacking heme (the apo form) cannot support caspase activation, although the reason for this has not been studied. Here we show that apocytochrome c still binds Apaf-1 and that it can block holo-dependent caspase activation in a cell-free system. In addition we show that overexpression of apocytochrome c blocks Bax-induced apoptosis in cells. Thus it is possible to modulate cell survival by interfering with the Apaf-1/cytochrome c interaction. Given the key role played by Apaf-1/cytochrome c in the apoptotic process, and the role of apoptosis in degenerative disease, this interaction may serve as a novel therapeutic target.
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