Heat shock response relieves ER stress

EMBO J. 2008 Apr 9;27(7):1049-59. doi: 10.1038/emboj.2008.42. Epub 2008 Mar 6.

Abstract

Accumulation of misfolded protein in the endoplasmic reticulum (ER) causes stress. The unfolded protein response (UPR), a transcriptional induction pathway, is activated to relieve ER stress. Although UPR is not essential for viability, UPR-deficient cells are more sensitive to ER stress; ire1Delta cells cannot grow when challenged with tunicamycin or by overexpression of misfolded CPY(*). In these cells, multiple functions are defective, including translocation, ER-associated degradation (ERAD), and ER-to-Golgi transport. We tested whether heat shock response (HSR) can relieve ER stress. Using a constitutively active Hsf1 transcription factor to induce HSR without temperature shift, we find that HSR rescues growth of stressed ire1Delta cells, and partially relieves defects in translocation and ERAD. Cargo-specific effects of constitutively active Hsf1 on ER-to-Golgi transport are correlated with enhanced protein levels of the respective cargo receptors. In vivo, HSR is activated by ER stress, albeit to a lower level than that caused by heat. Genomic analysis of HSR targets reveals that >25% have function in common with UPR targets. We propose that HSR can relieve stress in UPR-deficient cells by affecting multiple ER activities.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Biological Transport
  • COP-Coated Vesicles / metabolism
  • Carboxypeptidases / chemistry
  • Carboxypeptidases / metabolism
  • DNA-Binding Proteins / metabolism
  • Endoplasmic Reticulum / metabolism*
  • Endoplasmic Reticulum / pathology*
  • Genes, Fungal
  • Golgi Apparatus / metabolism
  • Heat Shock Transcription Factors
  • Heat-Shock Response / physiology*
  • Membrane Glycoproteins / metabolism
  • Membrane Proteins / metabolism
  • Microbial Viability
  • Models, Biological
  • Mutation / genetics
  • Protein Folding
  • Protein Processing, Post-Translational
  • Protein Serine-Threonine Kinases / metabolism
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism
  • Transcription Factors / metabolism
  • Vesicular Transport Proteins

Substances

  • DNA-Binding Proteins
  • Erv29 protein, S cerevisiae
  • Heat Shock Transcription Factors
  • Membrane Glycoproteins
  • Membrane Proteins
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Vesicular Transport Proteins
  • IRE1 protein, S cerevisiae
  • Protein Serine-Threonine Kinases
  • Carboxypeptidases
  • CPY protein, S cerevisiae