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Hsp27 inhibits cytochrome <i>c</i>-mediated caspase activation by sequestering both pro-caspase-3 and cytochrome <i>c</i>

Concannon, C.G.
; 
Orrenius, S.
; 
Samali, A.
Identifiers
http://hdl.handle.net/10379/8987
 https://doi.org/10.13025/23414
Publication Date
2001-04-01
Keywords
apoptosis, caspase, cytochrome c, hsp27, stress, heat-shock proteins, small stress proteins, cell-death, dependent activation, oxidative stress, apoptosis, mitochondria, release, bcl-2, procaspase-9
Type
Article
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Citation
Concannon, C.G. Orrenius, S.; Samali, A. (2001). Hsp27 inhibits cytochrome <i>c</i>-mediated caspase activation by sequestering both pro-caspase-3 and cytochrome <i>c</i>. Gene Expression 9 (4), 195-201
Abstract
Mitochondrial cytochrome c release in response to pro-apoptotic signals leads to the formation of a cytochrome c/Apaf-1/procaspase-9 complex (the apoptosome) and resultant activation of caspase-9 and caspase-3. Here we demonstrate that the molecular chaperone, Hsp27, inhibits this cytochrome c-mediated activation of caspase-3. Immunodepeletion of Hsp27 from cytochrome c-activated cytosols resulted in decreased caspase activity. Furthermore, immunoprecipitation of Hsp27 resulted in the coprecipitation of both cytochrome c and procaspase-3. In reciprocal experiments, immunoprecipitation of both procaspase-3 and cytochrome c resulted in coprecipitation of Hsp27, indicating two independent interactions. These results point to Hsp27 mediating its inhibition of procaspase-3 activation through its ability to sequester both cytochrome c and procaspase-3, and thus prevent the correct formation/function of the apoptosome complex.
Funder
Publisher
Cognizant, LLC
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Rights
Attribution-NonCommercial-NoDerivs 3.0 Ireland
cbn
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Externally hosted open access publications with University of Galway authors (1)