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. 1996 Apr;1(1):33–39. doi: 10.1379/1466-1268(1996)001<0033:efaroh>2.3.co;2

Evidence for a role of Hsp 70 in the regulation of the heat shock response in mammalian cells

Ruben Baler 1, Jianying Zou 2, Richard Voellmy 2
PMCID: PMC313015  PMID: 9222587

Abstract

Heat and other environmental insults (stress) cause unfolding of proteins, triggering the activation of heat shock transcription factor HSF (HSF 1 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 complete with monomeric HSF1 for Hsp70 binding. This competetion would result in dissociation of an HSF1-Hsp70 complex, allowing trimerization of released HSF 1 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.

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