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PMID: 17024176 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A novel HSF1-mediated death pathway that is suppressed by heat shock proteins.

The EMBO journal ·Vol. 25 ·No. 20 ·2006-10-18 ·Pages 4773-83

Hayashida N, Inouye S, Fujimoto M, Tanaka Y, Izu H, Takaki E, Ichikawa H, Rho J, Nakai A

Abstract

Heat shock response is an adoptive response to proteotoxic stress, and a major heat shock transcription factor 1 (HSF1) has been believed to protect cells from cell death by inducing heat shock proteins (Hsps) that assist protein folding and prevent protein denaturation. However, it is revealed recently that HSF1 also promotes cell death of male germ cells. Here, we found a proapoptotic Tdag51 (T-cell death associated gene 51) gene as a direct target gene of HSF1. Heat shock and other stresses induced different levels of Hsps and Tdag51, which depend on cell types. Hsps bound directly to the N-terminal pleckstrin-homology like (PHL) domain of Tdag51, and suppressed death activity of the C-terminal proline/glutamine/histidine-rich domain. Tdag51, but not major Hsps, were induced in male germ cells exposed to high temperatures. Analysis of Tdag51-null testes showed that Tdag51 played substantial roles in promoting heat shock-induced cell death in vivo. These data suggest that cell fate on proteotoxic condition is determined at least by balance between Hsp and Tdag51 levels, which are differently regulated by HSF1.

MeSH Terms
Animals Cell Death/genetics DNA-Binding Proteins/deficiency,metabolism HeLa Cells Heat Shock Transcription Factors Heat-Shock Proteins/genetics,metabolism Hot Temperature Humans Male Mice Mice, Mutant Strains Protein Binding Protein Structure, Tertiary/genetics Signal Transduction/genetics Spermatozoa/metabolism Stress, Physiological/genetics,metabolism Testis/metabolism Transcription Factors/deficiency,genetics,metabolism
Chemicals
DNA-Binding Proteins Heat Shock Transcription Factors Heat-Shock Proteins Hsf1 protein, mouse Phlda1 protein, mouse Transcription Factors
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Hayashida Naoki
Department of Biochemistry and Molecular Biology, Yamaguchi University School of Medicine, Ube, Japan.
Inouye Sachiye
Fujimoto Mitsuaki
Tanaka Yasunori
Izu Hanae
Takaki Eiichi
Ichikawa Hitoshi
Rho Jaerang
Nakai Akira
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7601370
Published
2006-10-18
Epub
2006-00-05
Pages
4773-83
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1618102
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.emboj.7601370 PMC Full Text View journal details
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