Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/109930
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dc.contributor.authorLaço, Mário N.-
dc.contributor.authorCortes, Luísa-
dc.contributor.authorTravis, Sue M.-
dc.contributor.authorPaulson, Henry L.-
dc.contributor.authorRego, A. Cristina-
dc.date.accessioned2023-11-07T12:07:36Z-
dc.date.available2023-11-07T12:07:36Z-
dc.date.issued2012-
dc.identifier.issn1932-6203pt
dc.identifier.urihttp://hdl.handle.net/10316/109930-
dc.description.abstractAlterations in the ubiquitin-proteasome system (UPS) have been reported in several neurodegenerative disorders characterized by protein misfolding and aggregation, including the polylgutamine diseases. Machado-Joseph disease (MJD) or Spinocerebellar Ataxia type 3 is caused by a polyglutamine-encoding CAG expansion in the ATXN3 gene, which encodes a 42 kDa deubiquitinating enzyme (DUB), ataxin-3. We investigated ataxin-3 deubiquitinating activity and the functional relevance of ataxin-3 interactions with two proteins previously described to interact with ataxin-3, hHR23A and valosin-containing protein (VCP/p97). We confirmed ataxin-3 affinity for both hHR23A and VCP/p97. hHR23A and ataxin-3 were shown to co-localize in discrete nuclear foci, while VCP/p97 was primarily cytoplasmic. hHR23A and VCP/p97 recombinant proteins were added, separately or together, to normal and expanded ataxin-3 in in vitro deubiquitination assays to evaluate their influence on ataxin-3 activity. VCP/p97 was shown to be an activator specifically of wild-type ataxin-3, exhibiting no effect on expanded ataxin-3, In contrast, we observed no significant alterations in ataxin-3 enzyme kinetics or substrate preference in the presence of hHR23A alone or in combination with VCP. Based on our results we propose a model where ataxin-3 normally functions with its interactors to specify the cellular fate of ubiquitinated proteins.pt
dc.language.isoengpt
dc.publisherPublic Library of Sciencept
dc.rightsopenAccesspt
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt
dc.subject.meshAdenosine Triphosphatasespt
dc.subject.meshAnimalspt
dc.subject.meshAtaxin-3pt
dc.subject.meshCOS Cellspt
dc.subject.meshCell Cycle Proteinspt
dc.subject.meshChlorocebus aethiopspt
dc.subject.meshDNA Repair Enzymespt
dc.subject.meshDNA-Binding Proteinspt
dc.subject.meshHumanspt
dc.subject.meshHydrolasespt
dc.subject.meshKineticspt
dc.subject.meshModels, Biologicalpt
dc.subject.meshMutant Proteinspt
dc.subject.meshNerve Tissue Proteinspt
dc.subject.meshNuclear Proteinspt
dc.subject.meshPeptide Hydrolasespt
dc.subject.meshProtein Bindingpt
dc.subject.meshRepressor Proteinspt
dc.subject.meshSubstrate Specificitypt
dc.subject.meshTrinucleotide Repeat Expansionpt
dc.subject.meshUbiquitinpt
dc.subject.meshValosin Containing Proteinpt
dc.titleValosin-containing protein (VCP/p97) is an activator of wild-type ataxin-3pt
dc.typearticle-
degois.publication.firstPagee43563pt
degois.publication.issue9pt
degois.publication.titlePLoS ONEpt
dc.peerreviewedyespt
dc.identifier.doi10.1371/journal.pone.0043563pt
degois.publication.volume7pt
dc.date.embargo2012-01-01*
uc.date.periodoEmbargo0pt
item.grantfulltextopen-
item.cerifentitytypePublications-
item.languageiso639-1en-
item.openairetypearticle-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.fulltextCom Texto completo-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.orcid0000-0003-0700-3776-
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais
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This item is licensed under a Creative Commons License Creative Commons