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Title: Stress sensor Ire1 deploys a divergent transcriptional program in response to lipid bilayer stress
Authors: Ho, Nurulain
Yap, Wei Sheng
Xu, Jiaming
Wu, Haoxi
Koh, Jhee Hong
Goh, Wilson Wen Bin
George, Bhawana
Chong, Shu Chen
Taubert, Stefan
Thibault, Guillaume
Keywords: Science::Biological sciences
Issue Date: 2020
Source: Ho, N., Yap, W. S., Xu, J., Wu, H., Koh, J. H., Goh, W. W. B., George, B., Chong, S. C., Taubert, S. & Thibault, G. (2020). Stress sensor Ire1 deploys a divergent transcriptional program in response to lipid bilayer stress. Journal of Cell Biology, 219(7).
Project: NRF2018NRFNSFC003SB-006
Journal: Journal of Cell Biology
Abstract: Membrane integrity at the endoplasmic reticulum (ER) is tightly regulated, and its disturbance is implicated in metabolic diseases. Using an engineered sensor that activates the unfolded protein response (UPR) exclusively when normal ER membrane lipid composition is compromised, we identified pathways beyond lipid metabolism that are necessary to maintain ER integrity in yeast and in C. elegans. To systematically validate yeast mutants that disrupt ER membrane homeostasis, we identified a lipid bilayer stress (LBS) sensor in the UPR transducer protein Ire1, located at the interface of the amphipathic and transmembrane helices. Furthermore, transcriptome and chromatin immunoprecipitation analyses pinpoint the UPR as a broad-spectrum compensatory response wherein LBS and proteotoxic stress deploy divergent transcriptional UPR programs. Together, these findings reveal the UPR program as the sum of two independent stress responses, an insight that could be exploited for future therapeutic intervention.
ISSN: 0021-9525
DOI: 10.1083/jcb.201909165
Rights: © 2020 Ho et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at
Fulltext Permission: open
Fulltext Availability: With Fulltext
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