NEDD8: A new ataxin-3 interactor
Autor(a) principal: | |
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Data de Publicação: | 2007 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/5324 |
Resumo: | Machado-Joseph disease (MJD/SCA3) is an autosomal dominant neurodegenerative disease caused by the expansion of a CAG tract in the coding portion of the ATXN3 gene. The presence of ubiquitin-positive aggregates of the defective protein in affected neurons is characteristic of this and most of the polyglutamine disorders. Recently, the accumulation of the neural precursor cell expressed developmentally downregulated 8 (NEDD8), a ubiquitin-like protein, in the inclusions of MJD brains was reported. Here, we report a new molecular interaction between wild-type ataxin-3 and NEDD8, using in vitro and in situ approaches. Furthermore, we show that this interaction is not dependent on the ubiquitin-interacting motifs in ataxin-3, since the presence of the Josephin domain is sufficient for the interaction to occur. The conservation of the interaction between the Caenorhabditis elegans ataxin-3 homologue (atx-3) and NEDD8 suggests its biological and functional relevance. Molecular docking studies of the NEDD8 molecule to the Josephin domain of ataxin-3 suggest that NEDD8 interacts with ataxin-3 in a substrate-like mode. In agreement, ataxin-3 displays deneddylase activity against a fluorogenic NEDD8 substrate. |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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NEDD8: A new ataxin-3 interactorPolyglutamineUbiquitinE3 ligaseNeurodegenerationMJD/SCA3Machado-Joseph disease (MJD/SCA3) is an autosomal dominant neurodegenerative disease caused by the expansion of a CAG tract in the coding portion of the ATXN3 gene. The presence of ubiquitin-positive aggregates of the defective protein in affected neurons is characteristic of this and most of the polyglutamine disorders. Recently, the accumulation of the neural precursor cell expressed developmentally downregulated 8 (NEDD8), a ubiquitin-like protein, in the inclusions of MJD brains was reported. Here, we report a new molecular interaction between wild-type ataxin-3 and NEDD8, using in vitro and in situ approaches. Furthermore, we show that this interaction is not dependent on the ubiquitin-interacting motifs in ataxin-3, since the presence of the Josephin domain is sufficient for the interaction to occur. The conservation of the interaction between the Caenorhabditis elegans ataxin-3 homologue (atx-3) and NEDD8 suggests its biological and functional relevance. Molecular docking studies of the NEDD8 molecule to the Josephin domain of ataxin-3 suggest that NEDD8 interacts with ataxin-3 in a substrate-like mode. In agreement, ataxin-3 displays deneddylase activity against a fluorogenic NEDD8 substrate.http://www.sciencedirect.com/science/article/B6T20-4PGY4KR-1/1/1fa5da8c83d1c67f4864d0738ff047e32007info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleaplication/PDFhttp://hdl.handle.net/10316/5324http://hdl.handle.net/10316/5324engBiochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1773:11 (2007) 1619-1627Ferro, AnabelaCarvalho, Ana LuísaTeixeira-Castro, AndreiaAlmeida, CarlaTomé, Ricardo J.Cortes, LuísaRodrigues, Ana-JoãoLogarinho, ElsaSequeiros, JorgeMacedo-Ribeiro, SandraMaciel, Patríciainfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2020-05-25T05:46:53Zoai:estudogeral.uc.pt:10316/5324Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:55:26.801312Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
NEDD8: A new ataxin-3 interactor |
title |
NEDD8: A new ataxin-3 interactor |
spellingShingle |
NEDD8: A new ataxin-3 interactor Ferro, Anabela Polyglutamine Ubiquitin E3 ligase Neurodegeneration MJD/SCA3 |
title_short |
NEDD8: A new ataxin-3 interactor |
title_full |
NEDD8: A new ataxin-3 interactor |
title_fullStr |
NEDD8: A new ataxin-3 interactor |
title_full_unstemmed |
NEDD8: A new ataxin-3 interactor |
title_sort |
NEDD8: A new ataxin-3 interactor |
author |
Ferro, Anabela |
author_facet |
Ferro, Anabela Carvalho, Ana Luísa Teixeira-Castro, Andreia Almeida, Carla Tomé, Ricardo J. Cortes, Luísa Rodrigues, Ana-João Logarinho, Elsa Sequeiros, Jorge Macedo-Ribeiro, Sandra Maciel, Patrícia |
author_role |
author |
author2 |
Carvalho, Ana Luísa Teixeira-Castro, Andreia Almeida, Carla Tomé, Ricardo J. Cortes, Luísa Rodrigues, Ana-João Logarinho, Elsa Sequeiros, Jorge Macedo-Ribeiro, Sandra Maciel, Patrícia |
author2_role |
author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Ferro, Anabela Carvalho, Ana Luísa Teixeira-Castro, Andreia Almeida, Carla Tomé, Ricardo J. Cortes, Luísa Rodrigues, Ana-João Logarinho, Elsa Sequeiros, Jorge Macedo-Ribeiro, Sandra Maciel, Patrícia |
dc.subject.por.fl_str_mv |
Polyglutamine Ubiquitin E3 ligase Neurodegeneration MJD/SCA3 |
topic |
Polyglutamine Ubiquitin E3 ligase Neurodegeneration MJD/SCA3 |
description |
Machado-Joseph disease (MJD/SCA3) is an autosomal dominant neurodegenerative disease caused by the expansion of a CAG tract in the coding portion of the ATXN3 gene. The presence of ubiquitin-positive aggregates of the defective protein in affected neurons is characteristic of this and most of the polyglutamine disorders. Recently, the accumulation of the neural precursor cell expressed developmentally downregulated 8 (NEDD8), a ubiquitin-like protein, in the inclusions of MJD brains was reported. Here, we report a new molecular interaction between wild-type ataxin-3 and NEDD8, using in vitro and in situ approaches. Furthermore, we show that this interaction is not dependent on the ubiquitin-interacting motifs in ataxin-3, since the presence of the Josephin domain is sufficient for the interaction to occur. The conservation of the interaction between the Caenorhabditis elegans ataxin-3 homologue (atx-3) and NEDD8 suggests its biological and functional relevance. Molecular docking studies of the NEDD8 molecule to the Josephin domain of ataxin-3 suggest that NEDD8 interacts with ataxin-3 in a substrate-like mode. In agreement, ataxin-3 displays deneddylase activity against a fluorogenic NEDD8 substrate. |
publishDate |
2007 |
dc.date.none.fl_str_mv |
2007 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/5324 http://hdl.handle.net/10316/5324 |
url |
http://hdl.handle.net/10316/5324 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1773:11 (2007) 1619-1627 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
aplication/PDF |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799133841665818624 |