Peer-Reviewed Journal Details
Mandatory Fields
Concannon, CG,Orrenius, S,Samali, A
2001
January
Gene Expression
Hsp27 inhibits cytochrome c-mediated caspase activation by sequestering both pro-caspase-3 and cytochrome c
Published
()
Optional Fields
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
9
195
201
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.
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