Hsp27 inhibits cytochrome c-mediated caspase activation by sequestering both pro-caspase-3 and cytochrome c

Gene Expr. 2001;9(4-5):195-201. doi: 10.3727/000000001783992605.


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.

MeSH terms

  • Apoptosis
  • Caspase 3
  • Caspase Inhibitors*
  • Caspases / metabolism*
  • Cytochrome c Group / metabolism*
  • Enzyme Activation
  • Enzyme Precursors / metabolism*
  • Heat-Shock Proteins / immunology
  • Heat-Shock Proteins / metabolism*
  • Humans
  • Jurkat Cells
  • Mitochondria / enzymology
  • Precipitin Tests
  • Protein Binding
  • Temperature


  • Caspase Inhibitors
  • Cytochrome c Group
  • Enzyme Precursors
  • Heat-Shock Proteins
  • CASP3 protein, human
  • Caspase 3
  • Caspases