Abstract
The cellular-stress response can mediate cellular protection through expression of heat-shock protein (Hsp) 70, which can interfere with the process of apoptotic cell death. Stress-induced apoptosis proceeds through a defined biochemical process that involves cytochrome c, Apaf-1 and caspase proteases. Here we show, using a cell-free system, that Hsp70 prevents cytochrome c/dATP-mediated caspase activation, but allows the formation of Apaf-1 oligomers. Hsp70 binds to Apaf-1 but not to procaspase-9, and prevents recruitment of caspases to the apoptosome complex. Hsp70 therefore suppresses apoptosis by directly associating with Apaf-1 and blocking the assembly of a functional apoptosome.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Apoptosis*
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Apoptotic Protease-Activating Factor 1
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Binding Sites
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Caspase 9
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Caspases / chemistry
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Caspases / metabolism*
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Cell Line
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Cell-Free System
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Chromatography, Gel
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Cytochrome c Group / metabolism
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Deoxyadenine Nucleotides / antagonists & inhibitors
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Deoxyadenine Nucleotides / pharmacology
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Enzyme Activation / drug effects
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Enzyme Precursors / chemistry
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Enzyme Precursors / metabolism*
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HSP70 Heat-Shock Proteins / metabolism*
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Hot Temperature
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Humans
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Jurkat Cells
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Ligands
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Macromolecular Substances
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Protein Binding
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Protein Processing, Post-Translational
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Protein Structure, Tertiary
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Proteins / chemistry
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Proteins / metabolism*
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Recombinant Proteins / metabolism
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Substrate Specificity
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Transfection
Substances
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APAF1 protein, human
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Apoptotic Protease-Activating Factor 1
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Cytochrome c Group
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Deoxyadenine Nucleotides
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Enzyme Precursors
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HSP70 Heat-Shock Proteins
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Ligands
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Macromolecular Substances
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Proteins
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Recombinant Proteins
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CASP9 protein, human
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Caspase 9
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Caspases
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2'-deoxyadenosine triphosphate