Evidence for a role of Hsp70 in the regulation of the heat shock response in mammalian cells.
Heat and other environmental insults (stress) cause unfolding of proteins, triggering the activation of heat shock transcription factor HSF (HSF1 in vertebrates) that, in higher eukaryotes, involves trimerization of the factor and acquisition of heat shock element (HSE) DNA-binding ability. Interaction of activated HSF1 with HSEs in promoters of genes encoding heat shock proteins (Hsps) enhances their expression. It was suggested that Hsp70 may function as the negative regulator of HSF1. In the simplest model, stress-unfolded proteins would compete with monomeric HSF1 for Hsp70 binding. This competition would result in dissociation of an HSF1-Hsp70 complex, allowing trimerization of released HSF1 monomers. In support of this model, we present evidence herein that 1) non-activated HSF1 forms a 1:1 complex with Hsp70, 2) both rates of heat-induced appearance of HSF1 oligomers and rates of disappearance of HSF1 heterodimers and monomers decrease when concentrations of unengaged Hsps are increased, and 3) transient overexpression of Hsp70 inhibits heat activation of HSF1.
Baler
R
R
National Institutes of Health, Bethesda, MD 20592, USA.
Zou
J
J
Voellmy
R
R
D000818:Animals; D001667:Binding, Competitive; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D015870:Gene Expression; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism / Q000502:physiology*; D050884:HSP72 Heat-Shock Proteins; D006367:HeLa Cells; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D018869:Heat-Shock Response / Q000502:physiology*; D006801:Humans; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
D004268:DNA-Binding Proteins; D050883:HSC70 Heat-Shock Proteins; C000619706:HSF1 protein, human; D018840:HSP70 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; C494371:HSPA8 protein, human; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D014157:Transcription Factors