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

doi:10.1038/35019501

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

Molecular Biosciences

Research output: Contribution to journal › Article › peer-review

1356 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 language	English (US)
Pages (from-to)	469-475
Number of pages	7
Journal	Nature Cell Biology
Volume	2
Issue number	8
DOIs	https://doi.org/10.1038/35019501
State	Published - Aug 2000

Funding

ACKNOWLEDGEMENTS We thank G. Nunez and Y. Lazebnik for reagents, and C. Langlais and D. Brown for technical assistance. This work was supported by grants AI40646 and AI47891 from the National Institutes of Health. Correspondence and requests for materials should be addressed to D.R.G.

ASJC Scopus subject areas

Cell Biology

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@article{bff97bc79f794932878991361d817bf3,

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

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.",

author = "Beere, {Helen M.} and Wolf, {Beni B.} and Kelvin Cain and Mosser, {Dick D.} and Artin Mahboubi and Tomomi Kuwana and Pankaj Tailor and Morimoto, {Richard I.} and Cohen, {Gerald M.} and Green, {Douglas R.}",

note = "Funding Information: ACKNOWLEDGEMENTS We thank G. Nunez and Y. Lazebnik for reagents, and C. Langlais and D. Brown for technical assistance. This work was supported by grants AI40646 and AI47891 from the National Institutes of Health. Correspondence and requests for materials should be addressed to D.R.G.",

year = "2000",

month = aug,

doi = "10.1038/35019501",

language = "English (US)",

volume = "2",

pages = "469--475",

journal = "Nature Cell Biology",

issn = "1465-7392",

publisher = "Nature Research",

number = "8",

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T1 - Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome

AU - Beere, Helen M.

AU - Wolf, Beni B.

AU - Cain, Kelvin

AU - Mosser, Dick D.

AU - Mahboubi, Artin

AU - Kuwana, Tomomi

AU - Tailor, Pankaj

AU - Morimoto, Richard I.

AU - Cohen, Gerald M.

AU - Green, Douglas R.

N1 - Funding Information: ACKNOWLEDGEMENTS We thank G. Nunez and Y. Lazebnik for reagents, and C. Langlais and D. Brown for technical assistance. This work was supported by grants AI40646 and AI47891 from the National Institutes of Health. Correspondence and requests for materials should be addressed to D.R.G.

PY - 2000/8

Y1 - 2000/8

N2 - 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.

AB - 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.

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DO - 10.1038/35019501

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JO - Nature Cell Biology

JF - Nature Cell Biology

IS - 8

ER -

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

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