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dc.contributor.authorTheard, Delphine
dc.contributor.authorLabarrade, Florian
dc.contributor.authorPartisani, Mariagrazia
dc.contributor.authorMilanini, Julie
dc.contributor.authorSakagami, Hiroyuki
dc.contributor.authorFon, Edward A
dc.contributor.authorWood, Stephen A
dc.contributor.authorFranco, Michel
dc.contributor.authorLuton, Frederic
dc.date.accessioned2017-05-03T13:50:46Z
dc.date.available2017-05-03T13:50:46Z
dc.date.issued2010
dc.date.modified2011-03-07T08:55:54Z
dc.identifier.issn0261-4189
dc.identifier.doi10.1038/emboj.2010.46
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.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherNature Publishing Group
dc.publisher.placeUnited Kingdom
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom1499
dc.relation.ispartofpageto1509
dc.relation.ispartofissue9
dc.relation.ispartofjournalThe EMBO Journal
dc.relation.ispartofvolume29
dc.rights.retentionY
dc.subject.fieldofresearchBiological sciences
dc.subject.fieldofresearchAnimal cell and molecular biology
dc.subject.fieldofresearchInformation and computing sciences
dc.subject.fieldofresearchBiomedical and clinical sciences
dc.subject.fieldofresearchcode31
dc.subject.fieldofresearchcode310902
dc.subject.fieldofresearchcode46
dc.subject.fieldofresearchcode32
dc.titleUSP9x-mediated deubiquitination of EFA6 regulates de novo tight junction assembly
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.date.issued2010
gro.hasfulltextNo Full Text
gro.griffith.authorWood, Stephen A.


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