Editors' ChoiceApoptosis

Another Apoptosome

+ See all authors and affiliations

Science's STKE  17 Dec 2002:
Vol. 2002, Issue 163, pp. tw480-TW480
DOI: 10.1126/stke.2002.163.tw480

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.

S. H. Read, B. C. Baliga, P. G. Ekert, D. L. Vaux, S. Kumar, A novel Apaf-1-independent putative caspase-2 activation complex. J. Cell Biol. 159, 739-745 (2002). [Abstract] [Full Text]

Related Content