Heat shock response relieves ER stress

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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; ire1 Δ 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 ire1 Δ 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.