Sci. STKE, 17 December 2002
Apoptosis Another Apoptosome
Stress-induced apoptosis is achieved through a mitochondrial pathway that involves the release of cytochrome c from mitochondria into the cytosol. This event triggers the assembly of a protein complex called the Apaf-1 apoptosome, which then recruits and activates the intracellular protease caspase-9. Because caspase-2 has been reported to act both upstream of mitochondria and downstream of caspase-9, its mechanism of activation and its regulation have not been clear. Read et al. report that, like caspase-9, caspase-2 is recruited into a large protein complex, but that this is independent of cytochrome c and Apaf-1. Its presence in this large complex, as both procaspase-2 and as cleaved caspase-2, was detected by size exclusion chromatography of various cell extracts. The size of the caspase-2 protein complex is similar to that of the Apaf-1 apoptosome, and the associated caspase-2 is catalytically active. The authors propose that although procaspase-2 is cleaved and fully activated downstream of caspase-9, some initial activation may also occur without any enzymatic processing in the context of this apoptosome-like complex, upstream of mitochondria.
Citation: Another Apoptosome. Sci. STKE 2002, tw480 (2002).
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