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Hsp60 accelerates the maturation of pro‐caspase‐3 by upstream activator proteases during apoptosis
Author(s) -
Xanthoudakis Steven,
Roy Sophie,
Rasper Dita,
Hennessey Trevor,
Aubin Yves,
Cassady Robin,
Tawa Paul,
Ruel Rejean,
Rosen Antony,
Nicholson Donald W.
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.8.2049
Subject(s) - biology , proteases , caspase , activator (genetics) , apoptosis , microbiology and biotechnology , hsp60 , upstream (networking) , caspase 1 , heat shock protein , genetics , biochemistry , hsp70 , enzyme , gene , programmed cell death , computer network , computer science
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.