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dc.contributor.authorAmin-Wetzel, Niko
dc.contributor.authorNeidhardt, Lisa
dc.contributor.authorYan, Yahui
dc.contributor.authorMayer, Matthias P
dc.contributor.authorRon, David
dc.date.accessioned2020-02-04T05:16:09Z
dc.date.available2020-02-04T05:16:09Z
dc.date.issued2019-12-24
dc.date.submitted2019-08-02
dc.identifier.other50793
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/301704
dc.descriptionFunder: Medical Research Council; FundRef: http://dx.doi.org/10.13039/501100000265
dc.descriptionFunder: European Molecular Biology Organization; FundRef: http://dx.doi.org/10.13039/100004410
dc.description.abstractCoupling of endoplasmic reticulum (ER) stress to dimerisation-dependent activation of the UPR transducer IRE1 is incompletely understood. Whilst the luminal co-chaperone ERdj4 promotes a complex between the Hsp70 BiP and IRE1’s stress-sensing luminal domain (IRE1LD) that favours the latter’s monomeric inactive state and loss of ERdj4 de-represses IRE1, evidence linking these cellular and in vitro observations is presently lacking. We report that enforced loading of endogenous BiP onto endogenous IRE1α repressed UPR signalling in CHO cells and deletions in the IRE1α locus that de-repressed the UPR in cells, encode flexible regions of IRE1LD that mediated BiP-induced monomerisation in vitro. Changes in the hydrogen exchange mass spectrometry profile of IRE1LD induced by ERdj4 and BiP confirmed monomerisation and were consistent with active destabilisation of the IRE1LD dimer. Together, these observations support a competition model whereby waning ER stress passively partitions ERdj4 and BiP to IRE1LD to initiate active repression of UPR signalling.
dc.languageen
dc.publishereLife Sciences Publications, Ltd
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectResearch Article
dc.subjectCell Biology
dc.subjectIRE1
dc.subjectBiP/Grp78
dc.subjectendoplasmic reticulum (ER)
dc.subjectunfolded protein response (UPR)
dc.subjectERdj4/DNAJB9
dc.subjectChinese Hamster Ovary (CHO) cells
dc.subjectE. coli
dc.subjectOther
dc.titleUnstructured regions in IRE1α specify BiP-mediated destabilisation of the luminal domain dimer and repression of the UPR
dc.typeArticle
dc.date.updated2020-02-04T05:16:08Z
prism.publicationNameeLife, volume 8
dc.identifier.doi10.17863/CAM.48775
dcterms.dateAccepted2019-12-23
rioxxterms.versionofrecord10.7554/elife.50793
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
datacite.contributor.supervisoreditor: Hendershot, Linda M
datacite.contributor.supervisorsenior_editor: Malhotra, Vivek
dc.contributor.orcidAmin-Wetzel, Niko [0000-0002-4640-3724]
dc.contributor.orcidNeidhardt, Lisa [0000-0003-0256-5040]
dc.contributor.orcidYan, Yahui [0000-0001-6934-9874]
dc.contributor.orcidMayer, Matthias P [0000-0002-7859-3112]
dc.contributor.orcidRon, David [0000-0002-3014-5636]
dc.identifier.eissn2050-084X
pubs.funder-project-idDeutsche Forschungsgemeinschaft (SFB1036 TP9)
pubs.funder-project-idWellcome (Wellcome 996 100140)
pubs.funder-project-idWellcome (Wellcome 200848/Z/16/Z)
pubs.funder-project-idDeutsche Forschungsgemeinschaft (MA 1278/4-3)


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY 4.0)