Negative regulation of the heat shock transcriptional response by HSBP1

Genes Dev. 1998 Jul 1;12(13):1962-74. doi: 10.1101/gad.12.13.1962.

Abstract

In response to stress, heat shock factor 1 (HSF1) acquires rapid DNA binding and transient transcriptional activity while undergoing conformational transition from an inert non-DNA-binding monomer to active functional trimers. Attenuation of the inducible transcriptional response occurs during heat shock or upon recovery at non-stress conditions and involves dissociation of the HSF1 trimer and loss of activity. We have used the hydrophobic repeats of the HSF1 trimerization domain in the yeast two-hybrid protein interaction assay to identify heat shock factor binding protein 1 (HSBP1), a novel, conserved, 76-amino-acid protein that contains two extended arrays of hydrophobic repeats that interact with the HSF1 heptad repeats. HSBP1 is nuclear-localized and interacts in vivo with the active trimeric state of HSF1 that appears during heat shock. During attenuation of HSF1 to the inert monomer, HSBP1 associates with Hsp70. HSBP1 negatively affects HSF1 DNA-binding activity, and overexpression of HSBP1 in mammalian cells represses the transactivation activity of HSF1. To establish a biological role for HSBP1, the homologous Caenorhabditis elegans protein was overexpressed in body wall muscle cells and was shown to block activation of the heat shock response from a heat shock promoter-reporter construct. Alteration in the level of HSBP1 expression in C. elegans has severe effects on survival of the animals after thermal and chemical stress, consistent with a role for HSBP1 as a negative regulator of the heat shock response.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Caenorhabditis elegans / drug effects
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / growth & development
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Dogs
  • HSP70 Heat-Shock Proteins / metabolism
  • HeLa Cells
  • Heat Shock Transcription Factors
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism
  • Heat-Shock Proteins / physiology*
  • Heat-Shock Response / genetics
  • Heat-Shock Response / physiology*
  • Humans
  • Kidney / cytology
  • Mice
  • Molecular Sequence Data
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Nuclear Proteins / physiology*
  • Repetitive Sequences, Nucleic Acid
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Repressor Proteins / physiology*
  • Reticulocytes
  • Subcellular Fractions / metabolism
  • Transcription Factors
  • Transcription, Genetic / physiology*
  • Transcriptional Activation

Substances

  • DNA-Binding Proteins
  • HSBP1 protein, human
  • HSF1 protein, human
  • HSP70 Heat-Shock Proteins
  • Heat Shock Transcription Factors
  • Heat-Shock Proteins
  • Nuclear Proteins
  • Repressor Proteins
  • Transcription Factors

Associated data

  • GENBANK/AF068754