Hsp27 Inhibits Cytochrome c-Mediated Caspase Activation by Sequestering Both Pro-caspase-3 and Cytochrome c

Authors: CONCANNON C.G.¹; ORRENIUS S.²; SAMALI A.¹

Source: Gene Expression, Volume 9, Numbers 4-5, 2001 , pp. 195-201(7)

Publisher: Cognizant Communication Corporation

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.

Keywords: Apoptosis Caspase Cytochrome c Hsp27 Stress

Language: English

Document Type: Research article

Affiliations: 1: *Cell Stress and Apoptosis Research Group, Department of Biochemistry, National University of Ireland, Galway, Ireland 2: †Institute of Environmental Medicine, Karolinska Institutet, Box 210, S-171 77, Stockholm, Sweden

Publication date: 2001-01-01

• The Molecular and Cellular Biology area of Gene Expression covers all aspects of the gene including it structure, functions, and regulation in prokaryotes, eukaryotes, and viruses; molecular and cell biological aspects of cell growth and development, chromatin structure and function. These include topics such as DNA replication, DNA repair, gene transcription, transcriptional control, RNA processing, posttranscriptional control, oncogenes, molecular mechanisms of action of hormones, molecular mechanism of cellular differentiation, growth and development, protein synthesis, and posttranslational control.
  The Molecular and Cellular Neuroscience area of Gene Expression covers all aspects of gene expression as described but is devoted exclusively to the nervous system in health and disease. Topics include studies of neurogenesis, development, aging, and neurodegeneration. Complex neural systems, motor control, special senses, and higher cortical function, when viewed from the perspective of gene expression, are appropriate for the journal. Research related to molecular mechanisms of drug tolerance, dependence, and withdrawal are solicited. Manuscripts on state-of-the-art methods and protocols for molecular profiling of neuronal structure and function are welcome.

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• In this Subject: Biotechnology ,  Genetics
• By this author: CONCANNON C.G. ;  ORRENIUS S. ;  SAMALI A.

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