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

Jin Hou (Institutionen för kemi- och bioteknik, Systembiologi) ; H. T. Tang ; Zihe Liu (Institutionen för kemi- och bioteknik, Systembiologi) ; Tobias Österlund (Institutionen för kemi- och bioteknik, Systembiologi) ; Jens B. Nielsen (Institutionen för kemi- och bioteknik, Systembiologi) ; Dina Petranovic (Institutionen för kemi- och bioteknik, Systembiologi)
Fems Yeast Research (1567-1356). Vol. 14 (2014), 3, p. 481-494.
[Artikel, refereegranskad vetenskaplig]

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.

Nyckelord: heat shock response, endoplasmic reticulum stress, oxidative stress response, proteasome activity, transcriptome analysis, UNFOLDED PROTEIN RESPONSE, ER-ASSOCIATED DEGRADATION, GENOME-WIDE, ANALYSIS, SACCHAROMYCES-CEREVISIAE, TRANSCRIPTION FACTOR, OXIDATIVE, STRESS, QUALITY-CONTROL, IN-VIVO, EXPRESSION, HSF1



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Denna post skapades 2014-06-23. Senast ändrad 2017-01-17.
CPL Pubid: 199461

 

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Institutioner (Chalmers)

Institutionen för kemi- och bioteknik, Systembiologi (2008-2014)

Ämnesområden

Livsvetenskaper
Mikrobiologi

Chalmers infrastruktur

C3SE/SNIC (Chalmers Centre for Computational Science and Engineering)

 


Projekt

Denna publikation är ett resultat av följande projekt:


Industrial Systems Biology of Yeast and A. oryzae (INSYSBIO) (EC/FP7/247013)