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dc.contributor.authorKanekura, Kohsuke
dc.contributor.authorMa, Xiucui
dc.contributor.authorMurphy, John T.
dc.contributor.authorZhu, Lihua Julie
dc.contributor.authorDiwan, Abhinav
dc.contributor.authorUrano, Fumihiko
dc.date2022-08-11T08:09:19.000
dc.date.accessioned2022-08-23T16:26:20Z
dc.date.available2022-08-23T16:26:20Z
dc.date.issued2015-06-23
dc.date.submitted2015-12-03
dc.identifier.citationSci Signal. 2015 Jun 23;8(382):ra62. doi: 10.1126/scisignal.aaa0341. <a href="http://dx.doi.org/10.1126/scisignal.aaa0341">Link to article on publisher's site</a>
dc.identifier.issn1937-9145 (Electronic)
dc.identifier.doi10.1126/scisignal.aaa0341
dc.identifier.pmid26106220
dc.identifier.urihttp://hdl.handle.net/20.500.14038/36544
dc.description.abstractThe endoplasmic reticulum (ER) has emerged as a critical regulator of cell survival. IRE1 is a transmembrane protein with kinase and RNase activities that is localized to the ER and that promotes resistance to ER stress. We showed a mechanism by which IRE1 conferred protection against ER stress-mediated cell death. IRE1 signaling prevented ER membrane permeabilization mediated by Bax and Bak and cell death in cells experiencing ER stress. Suppression of IRE1 signaling triggered by its kinase activity led to the accumulation of the BH3 domain-containing protein Bnip3, which in turn triggered the oligomerization of Bax and Bak in the ER membrane and ER membrane permeabilization. Consequently, in response to ER stress, cells deficient in IRE1 were susceptible to leakage of ER contents, which was associated with the accumulation of calcium in mitochondria, oxidative stress in the cytosol, and ultimately cell death. Our results reveal a role for IRE1 in preventing a cell death-initializing step that emanates from the ER and provide a potential target for treating diseases characterized by ER stress, including diabetes and Wolfram syndrome.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=26106220&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4492519/
dc.subjectCell Biology
dc.subjectCellular and Molecular Physiology
dc.titleIRE1 prevents endoplasmic reticulum membrane permeabilization and cell death under pathological conditions
dc.typeJournal Article
dc.source.journaltitleScience signaling
dc.source.volume8
dc.source.issue382
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/mccb_pubs/40
dc.identifier.contextkey7899963
html.description.abstract<p>The endoplasmic reticulum (ER) has emerged as a critical regulator of cell survival. IRE1 is a transmembrane protein with kinase and RNase activities that is localized to the ER and that promotes resistance to ER stress. We showed a mechanism by which IRE1 conferred protection against ER stress-mediated cell death. IRE1 signaling prevented ER membrane permeabilization mediated by Bax and Bak and cell death in cells experiencing ER stress. Suppression of IRE1 signaling triggered by its kinase activity led to the accumulation of the BH3 domain-containing protein Bnip3, which in turn triggered the oligomerization of Bax and Bak in the ER membrane and ER membrane permeabilization. Consequently, in response to ER stress, cells deficient in IRE1 were susceptible to leakage of ER contents, which was associated with the accumulation of calcium in mitochondria, oxidative stress in the cytosol, and ultimately cell death. Our results reveal a role for IRE1 in preventing a cell death-initializing step that emanates from the ER and provide a potential target for treating diseases characterized by ER stress, including diabetes and Wolfram syndrome.</p>
dc.identifier.submissionpathmccb_pubs/40
dc.contributor.departmentDepartment of Molecular, Cell and Cancer Biology
dc.source.pagesra62


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