Home LiteratureArticle Details

PMID: 10934466 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

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

Nature cell biology ·Vol. 2 ·No. 8 ·2000-08-00 ·Pages 469-75

Beere HM, Wolf BB, Cain K, Mosser DD, Mahboubi A, Kuwana T, Tailor P, Morimoto RI, Cohen GM, Green DR

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.

MeSH Terms

Apoptosis Apoptotic Protease-Activating Factor 1 Binding Sites Caspase 9 Caspases/chemistry,metabolism Cell Line Cell-Free System Chromatography, Gel Cytochrome c Group/metabolism Deoxyadenine Nucleotides/antagonists & inhibitors,pharmacology Enzyme Activation/drug effects Enzyme Precursors/chemistry,metabolism HSP70 Heat-Shock Proteins/metabolism Hot Temperature Humans Jurkat Cells Ligands Macromolecular Substances Protein Binding Protein Processing, Post-Translational Protein Structure, Tertiary Proteins/chemistry,metabolism Recombinant Proteins/metabolism Substrate Specificity Transfection

Chemicals

APAF1 protein, human Apoptotic Protease-Activating Factor 1 Cytochrome c Group Deoxyadenine Nucleotides Enzyme Precursors HSP70 Heat-Shock Proteins Ligands Macromolecular Substances Proteins Recombinant Proteins CASP9 protein, human Caspase 9 Caspases 2'-deoxyadenosine triphosphate

Authors & Affiliations

10 authors, click to expand affiliations / ORCID

Beere H M

La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, California 92121, USA.

Wolf B B

Cain K

Mosser D D

Mahboubi A

Kuwana T

Tailor P

Morimoto R I

Cohen G M

Green D R

Article Info

Journal

Nature cell biology

Abbr.

Nat Cell Biol

ISSN

1465-7392

DOI

10.1038/35019501

Published

2000-08-00

Pages

469-75

Language

English

Region

England

NLM ID

100890575

Subset

Grants

NIAID NIH HHS · AI40646 · United States

NIAID NIH HHS · AI47891 · United States

External Links

PubMed source DOI: 10.1038/35019501 View journal details

Analysis Services

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

Contact

WeChat Official Account