Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/67549

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dc.contributor.authorRodrigues, Ana Joãopor
dc.contributor.authorCosta, Maria do Carmopor
dc.contributor.authorSilva, Teresa Lpor
dc.contributor.authorFerreira, Danielapor
dc.contributor.authorBajanca, Fernandapor
dc.contributor.authorSantos, Elsa Clara Carvalho Logarinhopor
dc.contributor.authorMaciel, P.por
dc.date.accessioned2020-10-16T15:24:10Z-
dc.date.issued2010-10-
dc.identifier.issn0167-4889-
dc.identifier.urihttp://hdl.handle.net/1822/67549-
dc.description.abstractAtaxin-3 (ATXN3) is a widely expressed protein that binds to ubiquitylated proteins, has deubiquitylating activity in vitro and is thought to modulate substrate degradation through the ubiquitin-proteasome pathway. Expansion of a polyglutamine tract in ATXN3 causes Machado-Joseph disease, a late-onset neurodegenerative disorder characterized by ubiquitin-positive aggregate formation and specific neuronal death. Although ATXN3 has been involved in transcriptional repression and in the ubiquitin-proteasome pathway, its biological function is still unknown. In this work, we show that depletion of ATXN3 using small-interference RNA (siRNA) causes a prominent phenotype in both human and mouse cell lines. A mild increase in ubiquitylation occurs and cells exhibit ubiquitin-positive foci, which is consistent with ATXN3 putative function as a deubiquitylating enzyme. In addition, siATXN3-silenced cells exhibit marked morphological changes such as rounder shape and loss of adhesion protrusions. At a structural level, the microtubule, microfilament and intermediate filament networks are severely compromised and disorganized. This cytoskeletal phenotype is reversible and dependent on ATXN3 levels. Cell-extracellular matrix connection is also affected in ATXN3-depleted cells as talin expression is reduced in the focal adhesions and lower levels of alpha-1 integrin subunit are expressed at their surface. Although the cytoskeletal and adhesion problems do not originate any major change in the cell cycle of siATXN3-depleted cells, cell death is increased in siATXN3 cultures compared to controls. In summary, in this work we show that the absence of ATXN3 leads to an overt cytoskeletal/adhesion defect raising the possibility that this protein may play a role in the cytoskeleton.por
dc.description.sponsorshipAuthors would like to thank Agostinho Almeida for the help in theflow cytometry and Paula Ludovico for critical comments on themanuscript. AJR and MCC would like to thank all members of the PM labfor helpful discussions. This work wasfinanced by the Fundação para aCiência e a Tecnologia (FCT) (POCI/SAU-MMO/60412/2004). AJR, MCCand TS were supported by the FCT fellowships SFRH/BD/17066/2004,SFRH/BD/9759/2003 and SFRH/BI/33504/2008, respectively.por
dc.language.isoengpor
dc.publisherElsevierpor
dc.relationinfo:eu-repo/grantAgreement/FCT/POCI/60412/PTpor
dc.relationinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F17066%2F2004/PTpor
dc.relationinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F9759%2F2003/PTpor
dc.relationinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBI%2F33504%2F2008/PTpor
dc.rightsclosedAccesspor
dc.subject3T3 Cellspor
dc.subjectAnimalspor
dc.subjectApoptosispor
dc.subjectAtaxin-3por
dc.subjectBlotting, Westernpor
dc.subjectCell Cyclepor
dc.subjectCytoskeletonpor
dc.subjectFocal adhesionspor
dc.subjectHeLa Cellspor
dc.subjectHumanspor
dc.subjectIn situ nick-end labelingpor
dc.subjectIntegrin alpha1por
dc.subjectMicepor
dc.subjectMicroscopy, Confocalpor
dc.subjectNerve tissue proteinspor
dc.subjectNuclear proteinspor
dc.subjectRNA interferencepor
dc.subjectRepressor proteinspor
dc.subjectReverse transcriptase polymerase chain reactionpor
dc.subjectTranscription factorspor
dc.subjectPolyglutaminepor
dc.subjectUbiquitin-proteasomepor
dc.subjectSinocerebellar ataxia type 3por
dc.subjectTubulinpor
dc.titleAbsence of ataxin-3 leads to cytoskeletal disorganization and increased cell deathpor
dc.typearticlepor
dc.peerreviewedyespor
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S0167488910001989?via%3Dihubpor
oaire.citationStartPage1154por
oaire.citationEndPage1163por
oaire.citationIssue10por
oaire.citationVolume1803por
dc.identifier.essn1879-2596-
dc.identifier.doi10.1016/j.bbamcr.2010.07.004por
dc.date.embargo10000-01-01-
dc.identifier.pmid20637808por
dc.subject.wosScience & Technologypor
sdum.journalBiochimica et Biophysica Acta (BBA). Molecular Cell Researchpor
Appears in Collections:ICVS - Artigos em revistas internacionais / Papers in international journals

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