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dc.contributor.authorTheard, Delphineen_US
dc.contributor.authorLabarrade, Florianen_US
dc.contributor.authorPartisani, Mariagraziaen_US
dc.contributor.authorMilanini, Julieen_US
dc.contributor.authorSakagami, Hiroyukien_US
dc.contributor.authorFon, Edwarden_US
dc.contributor.authorWood, Stephenen_US
dc.contributor.authorFranco, Michelen_US
dc.contributor.authorLuton, Fredericen_US
dc.date.accessioned2017-05-03T13:50:46Z
dc.date.available2017-05-03T13:50:46Z
dc.date.issued2010en_US
dc.date.modified2011-03-07T08:55:54Z
dc.identifier.issn02614189en_US
dc.identifier.doi10.1038/emboj.2010.46en_AU
dc.identifier.urihttp://hdl.handle.net/10072/36934
dc.description.abstractIn epithelial cells, the tight junction (TJ) functions as a permeability barrier and is involved in cellular differentiation and proliferation. Although many TJ proteins have been characterized, little is known about the sequence of events and temporal regulation of TJ assembly in response to adhesion cues. We report here that the deubiquitinating enzyme USP9x has a critical function in TJ biogenesis by controlling the levels of the exchange factor for Arf6 (EFA6), a protein shown to facilitate TJ formation, during a narrow temporal window preceding the establishment of cell polarity. At steady state, EFA6 is constitutively ubiquitinated and turned over by the proteasome. However, at newly forming contacts, USP9x-mediated deubiquitination protects EFA6 from proteasomal degradation, leading to a transient increase in EFA6 levels. Consistent with this model, USP9x and EFA6 transiently co-localize at primordial epithelial junctions. Furthermore, knockdown of either EFA6 or USP9x impairs TJ biogenesis and EFA6 overexpression rescues TJ biogenesis in USP9x-knockdown cells. As the loss of cell polarity is a critical event in the metastatic spread of cancer, these findings may help to understand the pathology of human carcinomas.en_US
dc.description.peerreviewedYesen_US
dc.description.publicationstatusYesen_AU
dc.languageEnglishen_US
dc.language.isoen_AU
dc.publisherNature Publishing Groupen_US
dc.publisher.placeUnited Kingdomen_US
dc.relation.ispartofstudentpublicationNen_AU
dc.relation.ispartofpagefrom1499en_US
dc.relation.ispartofpageto1509en_US
dc.relation.ispartofissue9en_US
dc.relation.ispartofjournalThe EMBO Journalen_US
dc.relation.ispartofvolume29en_US
dc.rights.retentionYen_AU
dc.subject.fieldofresearchAnimal Cell and Molecular Biologyen_US
dc.subject.fieldofresearchcode060802en_US
dc.titleUSP9x-mediated deubiquitination of EFA6 regulates de novo tight junction assemblyen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.date.issued2010
gro.hasfulltextNo Full Text


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