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dc.rights.licenseopenen_US
hal.structure.identifierBordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
dc.contributor.authorHERAUD, Capucine
hal.structure.identifierBoRdeaux Institute in onCology [Inserm U1312 - BRIC]
dc.contributor.authorPINAULT, Mathilde
hal.structure.identifierBoRdeaux Institute in onCology [Inserm U1312 - BRIC]
dc.contributor.authorNEAUD, Veronique
IDREF: 202462633
hal.structure.identifierBoRdeaux Institute in onCology [Inserm U1312 - BRIC]
dc.contributor.authorSALTEL, Frédéric
ORCID: 0000-0002-0724-9680
IDREF: 089053079
hal.structure.identifierBoRdeaux Institute in onCology [Inserm U1312 - BRIC]
dc.contributor.authorLAGREE, Valerie
ORCID: 0000-0002-5334-4654
IDREF: 248905112
hal.structure.identifierBoRdeaux Institute in onCology [Inserm U1312 - BRIC]
dc.contributor.authorMOREAU, Violaine
ORCID: 0000-0002-4513-7022
IDREF: 110852656
dc.date.accessioned2023-01-20T12:00:36Z
dc.date.available2023-01-20T12:00:36Z
dc.date.issued2022-12-11
dc.identifier.issn1083-351Xen_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/171743
dc.description.abstractEnThe GTPase-activating protein (GAP) p190RhoGAP (p190A) is encoded by ARHGAP35 which is found mutated in cancers. p190A is a negative regulator of the GTPase RhoA in cells and must be targeted to RhoA-dependent actin-based structures to fulfill its roles. We previously identified a functional region of p190A called the PLS (protrusion localization sequence) required for localization of p190A to lamellipodia but also for regulating the GAP activity of p190A. Additional effects of the PLS region on p190A localization and activity need further characterization. Here, we demonstrated that the PLS is required to target p190A to invadosomes. Cellular expression of a p190A construct devoid of the PLS (p190AΔPLS) favored RhoA inactivation in a stronger manner than WT p190A, suggesting that the PLS is an autoinhibitory domain of p190A GAP activity. To decipher this mechanism, we searched for PLS-interacting proteins using a two-hybrid screen. We found that the PLS can interact with p190A itself. Coimmunoprecipitation experiments demonstrated that the PLS interacts with a region in close proximity to the GAP domain. Furthermore, we demonstrated that this interaction is abolished if the PLS harbors cancer-associated mutations: the S866F point mutation and the Δ865-870 deletion. Our results are in favor of defining PLS as an inhibitory domain responsible for masking the p190A functional GAP domain. Thus, p190A could exist in cells under two forms: an inactive closed conformation with a masked GAP domain and an open conformation allowing p190A GAP function. Altogether, our data unveil a new mechanism of p190A regulation.
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.subject.enGTPase-activating protein
dc.subject.enRho (Rho GTPase)
dc.subject.enConformational change
dc.subject.enMutant
dc.subject.enStructure-function
dc.subject.enActin
dc.subject.enCancer
dc.title.enIdentification of an inhibitory domain in GTPase-activating protein p190RhoGAP responsible for masking its functional GAP domain
dc.title.alternativeJ Biol Chemen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1016/j.jbc.2022.102792en_US
dc.subject.halSciences du Vivant [q-bio]/Canceren_US
dc.identifier.pubmed36516886en_US
bordeaux.journalJournal of Biological Chemistryen_US
bordeaux.page102792en_US
bordeaux.volume299en_US
bordeaux.hal.laboratoriesBRIC (Bordeaux of Institute of Oncology) - U1312en_US
bordeaux.issue1en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamEquipe 03 – Cancers du Foie et Invasion Tumoraleen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcepubmed
hal.identifierhal-03950650
hal.version1
hal.date.transferred2023-01-22T01:31:37Z
hal.exporttrue
workflow.import.sourcepubmed
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Journal%20of%20Biological%20Chemistry&rft.date=2022-12-11&rft.volume=299&rft.issue=1&rft.spage=102792&rft.epage=102792&rft.eissn=1083-351X&rft.issn=1083-351X&rft.au=HERAUD,%20Capucine&PINAULT,%20Mathilde&NEAUD,%20Veronique&SALTEL,%20Fr%C3%A9d%C3%A9ric&LAGREE,%20Valerie&rft.genre=article


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