A novel HSF1-mediated death pathway that is suppressed by heat shock proteins.
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.
Hayashida
Naoki
N
Department of Biochemistry and Molecular Biology, Yamaguchi University School of Medicine, Ube, Japan.
Inouye
Sachiye
S
Fujimoto
Mitsuaki
M
Tanaka
Yasunori
Y
Izu
Hanae
H
Takaki
Eiichi
E
Ichikawa
Hitoshi
H
Rho
Jaerang
J
Nakai
Akira
A
D000818:Animals; D016923:Cell Death / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000378:metabolism*; D006367:HeLa Cells; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D011485:Protein Binding; D017434:Protein Structure, Tertiary / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D013094:Spermatozoa / Q000378:metabolism*; D013312:Stress, Physiological / Q000235:genetics / Q000378:metabolism; D013737:Testis / Q000378:metabolism*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; C490017:Hsf1 protein, mouse; C114072:Phlda1 protein, mouse; D014157:Transcription Factors