Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/149106
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dc.contributor.authorHo, Nurulainen_US
dc.contributor.authorYap, Wei Shengen_US
dc.contributor.authorXu, Jiamingen_US
dc.contributor.authorWu, Haoxien_US
dc.contributor.authorKoh, Jhee Hongen_US
dc.contributor.authorGoh, Wilson Wen Binen_US
dc.contributor.authorGeorge, Bhawanaen_US
dc.contributor.authorChong, Shu Chenen_US
dc.contributor.authorTaubert, Stefanen_US
dc.contributor.authorThibault, Guillaumeen_US
dc.date.accessioned2021-05-24T01:43:24Z-
dc.date.available2021-05-24T01:43:24Z-
dc.date.issued2020-
dc.identifier.citationHo, 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). https://dx.doi.org/10.1083/jcb.201909165en_US
dc.identifier.issn0021-9525en_US
dc.identifier.urihttps://hdl.handle.net/10356/149106-
dc.description.abstractMembrane 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.en_US
dc.description.sponsorshipNanyang Technological Universityen_US
dc.description.sponsorshipNational Research Foundation (NRF)en_US
dc.language.isoenen_US
dc.relationNRF2018NRFNSFC003SB-006en_US
dc.relation.ispartofJournal of Cell Biologyen_US
dc.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 http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).en_US
dc.subjectScience::Biological sciencesen_US
dc.titleStress sensor Ire1 deploys a divergent transcriptional program in response to lipid bilayer stressen_US
dc.typeJournal Articleen
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.contributor.organizationInstitute of Molecular and Cell Biology, A*STARen_US
dc.identifier.doi10.1083/jcb.201909165-
dc.description.versionPublished versionen_US
dc.identifier.pmid32349127-
dc.identifier.issue7en_US
dc.identifier.volume219en_US
dc.subject.keywordsGeneticsen_US
dc.subject.keywordsMembrane and Lipid Biologyen_US
dc.description.acknowledgementThis work was supported by the Nanyang Assistant Professorship program from Nanyang Technological University (G. Thibault), the National Research Foundation Singapore under its National Research Foundation of Singapore together with the National Natural Science Foundation of China (NRF-NSFC) joint research grant call (NRF2018NRFNSFC003SB-006 to G. Thibault), the Nanyang Technological University Research Scholarship to N. Ho and J.H. Koh (predoctoral fellowship), the Natural Sciences and Engineering Research Council of Canada Discovery grant (RGPIN-2018-05133 to S. Taubert), the Canadian Institutes of Health Research (PJT-153199), and British Columbia Children's Hospital Research Institute (BCCHR) Canucks for Kids Graduate and University of British Columbia (UBC) Affiliate Studentships to J. Xu. Some strains were provided by the Caenorhabditis Genetic Center, which is funded by the National Institutes of Health Office of Research Infrastructure Programs (P40 OD010440).en_US
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