Repression of heat shock transcription factor HSF1 activation by HSP90 (HSP90 complex) that forms a stress-sensitive complex with HSF1.
Heat shock and other proteotoxic stresses cause accumulation of nonnative proteins that trigger activation of heat shock protein (Hsp) genes. A chaperone/Hsp functioning as repressor of heat shock transcription factor (HSF) could make activation of hsp genes dependent on protein unfolding. In a novel in vitro system, in which human HSF1 can be activated by nonnative protein, heat, and geldanamycin, addition of Hsp90 inhibits activation. Reduction of the level of Hsp90 but not of Hsp/c70, Hop, Hip, p23, CyP40, or Hsp40 dramatically activates HSF1. In vivo, geldanamycin activates HSF1 under conditions in which it is an Hsp90-specific reagent. Hsp90-containing HSF1 complex is present in the unstressed cell and dissociates during stress. We conclude that Hsp90, by itself and/or associated with multichaperone complexes, is a major repressor of HSF1.
Zou
J
J
Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, Florida 33101, USA.
Guo
Y
Y
Guettouche
T
T
Smith
D F
DF
Voellmy
R
R
D016227:Benzoquinones; D002474:Cell-Free System; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D000076249:Heat Shock Transcription Factors; D006801:Humans; D047029:Lactams, Macrocyclic; D008957:Models, Genetic; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation; D011489:Protein Denaturation; D011809:Quinones / Q000494:pharmacology; D012097:Repressor Proteins / Q000378:metabolism*; D017828:Rifabutin / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism*
D016227:Benzoquinones; D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D018841:HSP90 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D047029:Lactams, Macrocyclic; D011809:Quinones; D012097:Repressor Proteins; D014157:Transcription Factors; D017828:Rifabutin; C001277:geldanamycin