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dc.contributor.authorPeterson, Brian G
dc.contributor.authorGlaser, Morgan L
dc.contributor.authorRapoport, Tom A
dc.contributor.authorBaldridge, Ryan D
dc.date.accessioned2019-12-17T05:06:04Z
dc.date.available2019-12-17T05:06:04Z
dc.date.issued2019-11-12
dc.date.submitted2019-08-06
dc.identifier.issn2050-084X
dc.identifier.other50903
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/300009
dc.descriptionFunder: Howard Hughes Medical Institute; FundRef: http://dx.doi.org/10.13039/100000011
dc.description.abstractMisfolded proteins in the lumen of the endoplasmic reticulum (ER) are retrotranslocated into the cytosol and polyubiquitinated before being degraded by the proteasome. The multi-spanning ubiquitin ligase Hrd1 forms the retrotranslocation channel and associates with three other membrane proteins (Hrd3, Usa1, Der1) of poorly defined function. The Hrd1 channel is gated by autoubiquitination, but how Hrd1 escapes degradation by the proteasome and returns to its inactive ground state is unknown. Here, we show that autoubiquitination of Hrd1 is counteracted by Ubp1, a deubiquitinating enzyme that requires its N-terminal transmembrane segment for activity towards Hrd1. The Hrd1 partner Hrd3 serves as a brake for autoubiquitination, while Usa1 attenuates Ubp1's deubiquitination activity through an inhibitory effect of its UBL domain. These results lead to a model in which the Hrd1 channel is regulated by cycles of autoubiquitination and deubiquitination, reactions that are modulated by the other components of the Hrd1 complex.
dc.languageen
dc.publishereLife Sciences Publications, Ltd
dc.rightsAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectResearch Article
dc.subjectBiochemistry and Chemical Biology
dc.subjectCell Biology
dc.subjectERAD
dc.subjectprotein quality control
dc.subjectregulation
dc.subjectprotein degradation
dc.subjectS. cerevisiae
dc.titleCycles of autoubiquitination and deubiquitination regulate the ERAD ubiquitin ligase Hrd1.
dc.typeArticle
dc.date.updated2019-12-17T05:05:01Z
prism.publicationNameElife
dc.identifier.doi10.17863/CAM.47081
dcterms.dateAccepted2019-11-11
rioxxterms.versionofrecord10.7554/eLife.50903
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
datacite.contributor.supervisoreditor: Hegde, Ramanujan S
datacite.contributor.supervisorsenior_editor: Ron, David
dc.contributor.orcidPeterson, Brian G [0000-0001-6871-2336]
dc.contributor.orcidRapoport, Tom A [0000-0001-9911-4216]
dc.contributor.orcidBaldridge, Ryan D [0000-0001-7158-7812]
dc.identifier.eissn2050-084X
pubs.funder-project-idNational Institute of General Medical Sciences (R35GM128592)
pubs.funder-project-idNational Institute of General Medical Sciences (R01GM052586)
pubs.funder-project-idDamon Runyon Cancer Research Foundation (DRG-2184-14)
pubs.funder-project-idDamon Runyon Cancer Research Foundation (DFS-26-18)
pubs.funder-project-idUniversity of Michigan Medical School (Biological Sciences Scholars Program)
pubs.funder-project-idNational Institute of General Medical Sciences (Michigan Predoctoral Training in Genetics (T32GM007544))
cam.issuedOnline2019-11-12


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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)