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PMID: 11003656 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Inhibition of Daxx-mediated apoptosis by heat shock protein 27.

Molecular and cellular biology ·Vol. 20 ·No. 20 ·2000-10-00 ·Pages 7602-12

Charette SJ, Lavoie JN, Lambert H, Landry J

Abstract

Heat shock protein 27 (HSP27) confers cellular protection against a variety of cytotoxic stresses and also against physiological stresses associated with growth arrest or receptor-mediated apoptosis. Phosphorylation modulates the activity of HSP27 by causing a major change in the supramolecular organization of the protein, which shifts from oligomers to dimers. Here we show that phosphorylated dimers of HSP27 interact with Daxx, a mediator of Fas-induced apoptosis, preventing the interaction of Daxx with both Ask1 and Fas and blocking Daxx-mediated apoptosis. No such inhibition was observed with an HSP27 phosphorylation mutant that is only expressed as oligomers or when apoptosis was induced by transfection of a Daxx mutant lacking its HSP27 binding domain. HSP27 expression had no effect on Fas-induced FADD- and caspase-dependent apoptosis. However, HSP27 blocked Fas-induced translocation of Daxx from the nucleus to the cytoplasm and Fas-induced Daxx- and Ask1-dependent apoptosis. The observations revealed a new level of regulation of the Fas pathway and suggest a mechanism for the phosphorylation-dependent protective function of HSP27 during stress and differentiation.

MeSH Terms
Adaptor Proteins, Signal Transducing Amino Acid Chloromethyl Ketones/pharmacology Apoptosis/drug effects Arabidopsis Proteins Binding Sites Carrier Proteins/antagonists & inhibitors,genetics,metabolism Caspase Inhibitors Caspases/metabolism Cell Differentiation Cell Line Cell Nucleus/metabolism Co-Repressor Proteins Cytoplasm/metabolism Dimerization Fas-Associated Death Domain Protein Heat-Shock Proteins/genetics,metabolism Humans Intracellular Signaling Peptides and Proteins Kinetics Microscopy, Fluorescence Molecular Chaperones Mutation Nuclear Proteins Phosphorylation Plant Proteins/antagonists & inhibitors,genetics,metabolism Protein Binding Protein Transport Signal Transduction/drug effects Transfection Two-Hybrid System Techniques fas Receptor/genetics,metabolism
Chemicals
ASK1 protein, Arabidopsis Adaptor Proteins, Signal Transducing Amino Acid Chloromethyl Ketones Arabidopsis Proteins Carrier Proteins Caspase Inhibitors Co-Repressor Proteins DAXX protein, human FADD protein, human Fas-Associated Death Domain Protein Heat-Shock Proteins Intracellular Signaling Peptides and Proteins Molecular Chaperones Nuclear Proteins Plant Proteins benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone fas Receptor Caspases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Charette S J
Centre de Recherche en Cancérologie de l'Université Laval, L'Hôtel-Dieu de Québec, Québec, Canada G1R 2J6.
Lavoie J N
Lambert H
Landry J
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.20.20.7602-7612.2000
Published
2000-10-00
Pages
7602-12
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC86317
Subset
IM
Grants
Canadian Institutes of Health Research · 7088-4 · Canada
Canadian Institutes of Health Research · 7088-5 · Canada
Canadian Institutes of Health Research · 7088-6 · Canada
External Links
PubMed source DOI: 10.1128/MCB.20.20.7602-7612.2000 PMC Full Text View journal details
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