The human heat shock protein hsp70 interacts with HSF, the transcription factor that regulates heat shock gene expression

Klara Abravaya, Michael P. Myers, Shawn P. Murphy, Richard I. Morimoto*

*Corresponding author for this work

Research output: Contribution to journalArticle

397 Scopus citations

Abstract

Transcriptional regulation of the human hsp70 gene in response to heat shock and other forms of physiological stress occurs through the activation of heat shock transcription factor (HSF). Exposure of cells to a heat shock temperature of 42°C results in transient activation of HSF; its DNA-binding activity increases rapidly, plateaus, and attenuates, during which the intracellular levels of hsp70 increase. In an effort to understand whether HSF is regulated negatively by hsp70, we have examined whether HSF associates with hsp70. We show that activated HSF associates with hsp70 and that the interaction is detected as the levels of hsp70 increase in the cell. Addition of ATF and other hydrolyzable nucleotides results in the dissociation of hsp70 from HSF while nonhydrolyzable nucleotide analogs do not disrupt the complex. We demonstrate that exogenous recombinant wild-type hsp70 can associate with activated HSF, whereas no association is observed with an amino-terminal or a carboxy-terminal deletion mutant of hsp70. We also show that hsp70 blocks the in vitro activation of HSF from its cryptic non-DNA-binding state to a DNA-binding form; this inhibitory effect of hsp70 is abolished by ATF. We suggest that hsp70 may negatively regulate the activation of HSF.

Original languageEnglish (US)
Pages (from-to)1153-1164
Number of pages12
JournalGenes and Development
Volume6
Issue number7
DOIs
StatePublished - Jan 1 1992

Keywords

  • Heat shock protein
  • Heat shock transcription factor
  • Human hsp70 gene

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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