Heat shock response relieves ER stress.

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.
Mesh Terms:
Biological Transport, COP-Coated Vesicles, Carboxypeptidases, DNA-Binding Proteins, Endoplasmic Reticulum, Genes, Fungal, Golgi Apparatus, Heat-Shock Response, Membrane Glycoproteins, Membrane Proteins, Microbial Viability, Models, Biological, Mutation, Protein Folding, Protein Processing, Post-Translational, Protein-Serine-Threonine Kinases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Transcription Factors, Vesicular Transport Proteins
EMBO J.
Date: Apr. 09, 2008
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