Hyperactive TORC1 sensitizes yeast cells to endoplasmic reticulum stress by compromising cell wall integrity.
FEBS Lett. 2019 May 30;:
Authors: Ahmed K, Carter DE, Lajoie P
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 S. 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. This article is protected by copyright. All rights reserved.
PMID: 31144305 [PubMed - as supplied by publisher]