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https://hdl.handle.net/10356/149106
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DC Field | Value | Language |
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dc.contributor.author | Ho, Nurulain | en_US |
dc.contributor.author | Yap, Wei Sheng | en_US |
dc.contributor.author | Xu, Jiaming | en_US |
dc.contributor.author | Wu, Haoxi | en_US |
dc.contributor.author | Koh, Jhee Hong | en_US |
dc.contributor.author | Goh, Wilson Wen Bin | en_US |
dc.contributor.author | George, Bhawana | en_US |
dc.contributor.author | Chong, Shu Chen | en_US |
dc.contributor.author | Taubert, Stefan | en_US |
dc.contributor.author | Thibault, Guillaume | en_US |
dc.date.accessioned | 2021-05-24T01:43:24Z | - |
dc.date.available | 2021-05-24T01:43:24Z | - |
dc.date.issued | 2020 | - |
dc.identifier.citation | 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). https://dx.doi.org/10.1083/jcb.201909165 | en_US |
dc.identifier.issn | 0021-9525 | en_US |
dc.identifier.uri | https://hdl.handle.net/10356/149106 | - |
dc.description.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. | en_US |
dc.description.sponsorship | Nanyang Technological University | en_US |
dc.description.sponsorship | National Research Foundation (NRF) | en_US |
dc.language.iso | en | en_US |
dc.relation | NRF2018NRFNSFC003SB-006 | en_US |
dc.relation.ispartof | Journal of Cell Biology | en_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.subject | Science::Biological sciences | en_US |
dc.title | Stress sensor Ire1 deploys a divergent transcriptional program in response to lipid bilayer stress | en_US |
dc.type | Journal Article | en |
dc.contributor.school | School of Biological Sciences | en_US |
dc.contributor.organization | Institute of Molecular and Cell Biology, A*STAR | en_US |
dc.identifier.doi | 10.1083/jcb.201909165 | - |
dc.description.version | Published version | en_US |
dc.identifier.pmid | 32349127 | - |
dc.identifier.issue | 7 | en_US |
dc.identifier.volume | 219 | en_US |
dc.subject.keywords | Genetics | en_US |
dc.subject.keywords | Membrane and Lipid Biology | en_US |
dc.description.acknowledgement | This 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 |
item.fulltext | With Fulltext | - |
item.grantfulltext | open | - |
Appears in Collections: | SBS Journal Articles |
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File | Description | Size | Format | |
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jcb_201909165.pdf | 6.13 MB | Adobe PDF | View/Open |
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