Hyperactive TORC1 sensitizes yeast cells to endoplasmic reticulum stress by compromising cell wall integrity

被引：12

作者：

Ahmed, Khadija ^{[1
]}

Carter, David E. ^{[2
]}

Lajoie, Patrick ^{[1
]}

机构：

[1] Univ Western Ontario, Dept Anat & Cell Biol, London, ON N6A 5C1, Canada

[2] Univ Western Ontario, Robarts Res Inst, London, ON, Canada

来源：

FEBS LETTERS | 2019年 / 593卷 / 15期

基金：

加拿大创新基金会; 加拿大自然科学与工程研究理事会;

关键词：

caspofungin; cell wall integrity; endoplasmic reticulum stress; TORC1; unfolded protein response; UNFOLDED PROTEIN RESPONSE; SACCHAROMYCES-CEREVISIAE; TRANSCRIPTION FACTOR; DEGRADATION PATHWAY; GENE-EXPRESSION; MAMMALIAN HOST; ER STRESS; KINASE-C; RAPAMYCIN; MECHANISM;

D O I：

10.1002/1873-3468.13463

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Accumulation of misfolded proteins in the endoplasmic reticulum (ER) activates the unfolded protein response (UPR). Here, we investigated how the target of rapamycin complex 1 (TORC1) signaling cascade acts in parallel with the UPR to regulate ER stress sensitivity. Using Saccharomyces cerevisiae, we found that TORC1 signaling is attenuated during ER stress and constitutive activation of TORC1 increases sensitivity to ER stressors independently of the UPR. Transcriptome analysis revealed that TORC1 hyperactivation results in cell wall remodelling. Conversely, hyperactive TORC1 sensitizes cells to cell wall stressors, including the antifungal caspofungin. Elucidating the crosstalk between the UPR, cell wall integrity, and TORC1 signaling may uncover new paradigms through which the response to protein misfolding is regulated.

引用

页码：1957 / 1973

页数：17

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