Management of the endoplasmic reticulum stress by activation of the heat shock response in yeast

Jin Hou, Hongting Tang, Zihe Liu, Tobias Østerlund, Jens Nielsen, Dina Petranovic

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Abstract

In yeast Saccharomyces cerevisiae, accumulation of misfolded proteins in the
endoplasmic reticulum (ER) causes ER stress and activates the unfolded protein
response (UPR), which is mediated by Hac1p. The heat shock response
(HSR) mediated by Hsf1p, mainly regulates cytosolic processes and protects
the cell from stresses. Here, we find that a constitutive activation of the HSR
could increase ER stress resistance in both wild-type and UPR-deficient cells.
Activation of HSR decreased UPR activation in the WT (as shown by the
decreased HAC1 mRNA splicing). We analyzed the genome-wide transcriptional
response in order to propose regulatory mechanisms that govern the
interplay between UPR and HSR and followed up for the hypotheses by experiments
in vivo and in vitro. Interestingly, we found that the regulation of ER
stress response via HSR is (1) only partially dependent on over-expression of
Kar2p (ER resident chaperone induced by ER stress); (2) does not involve the
increase in protein turnover via the proteasome activity; (3) is related to the
oxidative stress response. From the transcription data, we also propose that
HSR enhances ER stress resistance mainly through facilitation of protein folding
and secretion. We also find that HSR coordinates multiple stress–response
pathways, including the repression of the overall transcription and translation.
Original languageEnglish
JournalF E M S Immunology and Medical Microbiology
Volume14
Issue number3
Pages (from-to)481-494
Number of pages15
ISSN0928-8244
DOIs
Publication statusPublished - 2014

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