Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome

Helen M. Beere, Beni B. Wolf, Kelvin Cain, Dick D. Mosser, Artin Mahboubi, Tomomi Kuwana, Pankaj Tailor, Richard I. Morimoto, Gerald M. Cohen, Douglas R. Green*

*Corresponding author for this work

Research output: Contribution to journalArticle

1193 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)469-475
Number of pages7
JournalNature Cell Biology
Volume2
Issue number8
DOIs
StatePublished - Aug 2000

ASJC Scopus subject areas

  • Cell Biology

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    Beere, H. M., Wolf, B. B., Cain, K., Mosser, D. D., Mahboubi, A., Kuwana, T., Tailor, P., Morimoto, R. I., Cohen, G. M., & Green, D. R. (2000). Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome. Nature Cell Biology, 2(8), 469-475. https://doi.org/10.1038/35019501