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. 1999 Apr 15;18(8):2049–2056. doi: 10.1093/emboj/18.8.2049

Hsp60 accelerates the maturation of pro-caspase-3 by upstream activator proteases during apoptosis.

S Xanthoudakis 1, S Roy 1, D Rasper 1, T Hennessey 1, Y Aubin 1, R Cassady 1, P Tawa 1, R Ruel 1, A Rosen 1, D W Nicholson 1
PMCID: PMC1171289  PMID: 10205159

Abstract

The activation of caspases represents a critical step in the pathways leading to the biochemical and morphological changes that underlie apoptosis. Multiple pathways leading to caspase activation appear to exist and vary depending on the death-inducing stimulus. We demonstrate that the activation of caspase-3, in Jurkat cells stimulated to undergo apoptosis by a Fas-independent pathway, is catalyzed by caspase-6. Caspase-6 was found to co-purify with caspase-3 as part of a multiprotein activation complex from extracts of camptothecin-treated Jurkat cells. A biochemical analysis of the protein constituents of the activation complex showed that Hsp60 was also present. Furthermore, an interaction between Hsp60 and caspase-3 could be demonstrated by co-immunoprecipitation experiments using HeLa as well as Jurkat cell extracts. Using a reconstituted in vitro system, Hsp60 was able to substantially accelerate the maturation of procaspase-3 by different upstream activator caspases and this effect was dependent on ATP hydrolysis. We propose that the ATP-dependent 'foldase' activity of Hsp60 improves the vulnerability of pro-caspase-3 to proteolytic maturation by upstream caspases and that this represents an important regulatory event in apoptotic cell death.

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Selected References

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