Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/109930
DC Field | Value | Language |
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dc.contributor.author | Laço, Mário N. | - |
dc.contributor.author | Cortes, Luísa | - |
dc.contributor.author | Travis, Sue M. | - |
dc.contributor.author | Paulson, Henry L. | - |
dc.contributor.author | Rego, A. Cristina | - |
dc.date.accessioned | 2023-11-07T12:07:36Z | - |
dc.date.available | 2023-11-07T12:07:36Z | - |
dc.date.issued | 2012 | - |
dc.identifier.issn | 1932-6203 | pt |
dc.identifier.uri | http://hdl.handle.net/10316/109930 | - |
dc.description.abstract | Alterations 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.iso | eng | pt |
dc.publisher | Public Library of Science | pt |
dc.rights | openAccess | pt |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt |
dc.subject.mesh | Adenosine Triphosphatases | pt |
dc.subject.mesh | Animals | pt |
dc.subject.mesh | Ataxin-3 | pt |
dc.subject.mesh | COS Cells | pt |
dc.subject.mesh | Cell Cycle Proteins | pt |
dc.subject.mesh | Chlorocebus aethiops | pt |
dc.subject.mesh | DNA Repair Enzymes | pt |
dc.subject.mesh | DNA-Binding Proteins | pt |
dc.subject.mesh | Humans | pt |
dc.subject.mesh | Hydrolases | pt |
dc.subject.mesh | Kinetics | pt |
dc.subject.mesh | Models, Biological | pt |
dc.subject.mesh | Mutant Proteins | pt |
dc.subject.mesh | Nerve Tissue Proteins | pt |
dc.subject.mesh | Nuclear Proteins | pt |
dc.subject.mesh | Peptide Hydrolases | pt |
dc.subject.mesh | Protein Binding | pt |
dc.subject.mesh | Repressor Proteins | pt |
dc.subject.mesh | Substrate Specificity | pt |
dc.subject.mesh | Trinucleotide Repeat Expansion | pt |
dc.subject.mesh | Ubiquitin | pt |
dc.subject.mesh | Valosin Containing Protein | pt |
dc.title | Valosin-containing protein (VCP/p97) is an activator of wild-type ataxin-3 | pt |
dc.type | article | - |
degois.publication.firstPage | e43563 | pt |
degois.publication.issue | 9 | pt |
degois.publication.title | PLoS ONE | pt |
dc.peerreviewed | yes | pt |
dc.identifier.doi | 10.1371/journal.pone.0043563 | pt |
degois.publication.volume | 7 | pt |
dc.date.embargo | 2012-01-01 | * |
uc.date.periodoEmbargo | 0 | pt |
item.grantfulltext | open | - |
item.cerifentitytype | Publications | - |
item.languageiso639-1 | en | - |
item.openairetype | article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.fulltext | Com Texto completo | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.orcid | 0000-0003-0700-3776 | - |
Appears in Collections: | FMUC Medicina - Artigos em Revistas Internacionais I&D CNC - Artigos em Revistas Internacionais |
Files in This Item:
File | Description | Size | Format | |
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ValosinContaining-Protein-VCPp97-Is-an-Activator-of-WildType-Ataxin3PLoS-ONE.pdf | 1.97 MB | Adobe PDF | View/Open |
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This item is licensed under a Creative Commons License