Publicação
ATX-3, CDC-48 and UBXN-5: a new trimolecular complex in Caenorhabditis elegans
| Resumo: | Ataxin-3 is the protein involved in Machado-Joseph disease, a neurodegenerative disorder caused by a polyglutamine expansion. Ataxin-3 binds ubiquitylated proteins and acts as a deubiquitylating enzyme in vitro. It was previously proposed that ataxin-3, along with the VCP/p97 protein, escorts ubiquitylated substrates for proteasomal degradation, although other players of this escort complex were not identified yet. In this work, we show that the Caenorhabditis elegans ataxin-3 protein (ATX-3) interacts with both VCP/p97 worm homologs, CDC-48.1 and CDC-48.2 and we map the interaction domains. We describe a motility defect in both ATX-3 and CDC-48.1 mutants and, in addition, we identify a new protein interactor, UBXN-5, potentially an adaptor of the CDC-48-ATX-3 escort complex. CDC-48 binds to both ATX-3 and UBXN-5 in a non-competitive manner, suggesting the formation of a trimolecular complex. Both CDC-48 and ATX-3, but not UBXN-5, were able to bind K-48 polyubiquitin chains, the standard signal for proteasomal degradation. Additionally, we describe several common interactors of ATX-3 and UBXN-5, some of which can be in vivo targets of this complex. |
|---|---|
| Autores principais: | Rodrigues, Ana João |
| Outros Autores: | Carvalho, Andreia Alexandra Neves; Ferro, Anabela; Rokka, Anne; Corthals, Garry; Logarinho, Elsa; Maciel, P. |
| Assunto: | Adaptor proteins, Signal transducing Adenosine triphosphatases Animals Ataxin-3 Caenorhabditis elegans Caenorhabditis elegans proteins Cell cycle proteins Multiprotein complexes Nerve tissue proteins Protein interaction domains and motifs Protein interaction mapping Valosin containing protein Polyglutamine Machado–Joseph disease Spinocerebellar ataxia type 3 Ubiquitin–proteasome pathway Deubiquitylating enzyme |
| Ano: | 2009 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso restrito |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| _version_ | 1867439183981707264 |
|---|---|
| author | Rodrigues, Ana João |
| author2 | Carvalho, Andreia Alexandra Neves Ferro, Anabela Rokka, Anne Corthals, Garry Logarinho, Elsa Maciel, P. |
| author2_role | author author author author author author |
| author_facet | Rodrigues, Ana João Carvalho, Andreia Alexandra Neves Ferro, Anabela Rokka, Anne Corthals, Garry Logarinho, Elsa Maciel, P. |
| author_role | author |
| contributor_name_str_mv | RepositóriUM - Universidade do Minho |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Rodrigues, Ana João\"},{\"Person.name\":\"Carvalho, Andreia Alexandra Neves\"},{\"Person.name\":\"Ferro, Anabela\"},{\"Person.name\":\"Rokka, Anne\"},{\"Person.name\":\"Corthals, Garry\"},{\"Person.name\":\"Logarinho, Elsa\"},{\"Person.name\":\"Maciel, P.\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | RepositóriUM - Universidade do Minho |
| datacite.creators.creator.creatorName.fl_str_mv | Rodrigues, Ana João Carvalho, Andreia Alexandra Neves Ferro, Anabela Rokka, Anne Corthals, Garry Logarinho, Elsa Maciel, P. |
| datacite.date.Accepted.fl_str_mv | 2009-09-01T00:00:00Z |
| datacite.date.embargoed.fl_str_mv | 10000-01-01T00:00:00Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_16ec |
| datacite.subjects.subject.fl_str_mv | Adaptor proteins, Signal transducing Adenosine triphosphatases Animals Ataxin-3 Caenorhabditis elegans Caenorhabditis elegans proteins Cell cycle proteins Multiprotein complexes Nerve tissue proteins Protein interaction domains and motifs Protein interaction mapping Valosin containing protein Polyglutamine Machado–Joseph disease Spinocerebellar ataxia type 3 Ubiquitin–proteasome pathway Deubiquitylating enzyme |
| datacite.titles.title.fl_str_mv | ATX-3, CDC-48 and UBXN-5: a new trimolecular complex in Caenorhabditis elegans |
| dc.contributor.none.fl_str_mv | RepositóriUM - Universidade do Minho |
| dc.creator.none.fl_str_mv | Rodrigues, Ana João Carvalho, Andreia Alexandra Neves Ferro, Anabela Rokka, Anne Corthals, Garry Logarinho, Elsa Maciel, P. |
| dc.date.Accepted.fl_str_mv | 2009-09-01T00:00:00Z |
| dc.date.embargoed.fl_str_mv | 10000-01-01T00:00:00Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | https://hdl.handle.net/1822/67644 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | Elsevier |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_16ec |
| dc.subject.none.fl_str_mv | Adaptor proteins, Signal transducing Adenosine triphosphatases Animals Ataxin-3 Caenorhabditis elegans Caenorhabditis elegans proteins Cell cycle proteins Multiprotein complexes Nerve tissue proteins Protein interaction domains and motifs Protein interaction mapping Valosin containing protein Polyglutamine Machado–Joseph disease Spinocerebellar ataxia type 3 Ubiquitin–proteasome pathway Deubiquitylating enzyme |
| dc.title.fl_str_mv | ATX-3, CDC-48 and UBXN-5: a new trimolecular complex in Caenorhabditis elegans |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | Ataxin-3 is the protein involved in Machado-Joseph disease, a neurodegenerative disorder caused by a polyglutamine expansion. Ataxin-3 binds ubiquitylated proteins and acts as a deubiquitylating enzyme in vitro. It was previously proposed that ataxin-3, along with the VCP/p97 protein, escorts ubiquitylated substrates for proteasomal degradation, although other players of this escort complex were not identified yet. In this work, we show that the Caenorhabditis elegans ataxin-3 protein (ATX-3) interacts with both VCP/p97 worm homologs, CDC-48.1 and CDC-48.2 and we map the interaction domains. We describe a motility defect in both ATX-3 and CDC-48.1 mutants and, in addition, we identify a new protein interactor, UBXN-5, potentially an adaptor of the CDC-48-ATX-3 escort complex. CDC-48 binds to both ATX-3 and UBXN-5 in a non-competitive manner, suggesting the formation of a trimolecular complex. Both CDC-48 and ATX-3, but not UBXN-5, were able to bind K-48 polyubiquitin chains, the standard signal for proteasomal degradation. Additionally, we describe several common interactors of ATX-3 and UBXN-5, some of which can be in vivo targets of this complex. |
| dirty | 0 |
| eu_rights_str_mv | restrictedAccess |
| format | article |
| fulltext.url.fl_str_mv | https://repositorium.uminho.pt/bitstreams/3e3d8092-0214-4dbe-8045-fcc0906799fc/download |
| id | rum_c0058cd00ca2ef8d495cfe5b653de6a8 |
| identifier.url.fl_str_mv | https://hdl.handle.net/1822/67644 |
| instacron_str | repositorium |
| institution | Universidade do Minho |
| instname_str | Universidade do Minho |
| language | eng |
| network_acronym_str | rum |
| network_name_str | RepositóriUM - Universidade do Minho |
| oai_identifier_str | oai:repositorium.uminho.pt:1822/67644 |
| organization_str_mv | urn:organizationAcronym:repositorium |
| person_str_mv | Rodrigues, Ana João Carvalho, Andreia Alexandra Neves Ferro, Anabela Rokka, Anne Corthals, Garry Logarinho, Elsa Maciel, P. |
| publishDate | 2009 |
| publisher.none.fl_str_mv | Elsevier |
| reponame_str | RepositóriUM - Universidade do Minho |
| repository_id_str | urn:repositoryAcronym:rum |
| service_str_mv | urn:repositoryAcronym:rum |
| spelling | engElsevierporAtaxin-3 is the protein involved in Machado-Joseph disease, a neurodegenerative disorder caused by a polyglutamine expansion. Ataxin-3 binds ubiquitylated proteins and acts as a deubiquitylating enzyme in vitro. It was previously proposed that ataxin-3, along with the VCP/p97 protein, escorts ubiquitylated substrates for proteasomal degradation, although other players of this escort complex were not identified yet. In this work, we show that the Caenorhabditis elegans ataxin-3 protein (ATX-3) interacts with both VCP/p97 worm homologs, CDC-48.1 and CDC-48.2 and we map the interaction domains. We describe a motility defect in both ATX-3 and CDC-48.1 mutants and, in addition, we identify a new protein interactor, UBXN-5, potentially an adaptor of the CDC-48-ATX-3 escort complex. CDC-48 binds to both ATX-3 and UBXN-5 in a non-competitive manner, suggesting the formation of a trimolecular complex. Both CDC-48 and ATX-3, but not UBXN-5, were able to bind K-48 polyubiquitin chains, the standard signal for proteasomal degradation. Additionally, we describe several common interactors of ATX-3 and UBXN-5, some of which can be in vivo targets of this complex.application/pdfporATX-3, CDC-48 and UBXN-5: a new trimolecular complex in Caenorhabditis elegansRodrigues, Ana JoãoCarvalho, Andreia Alexandra NevesFerro, AnabelaRokka, AnneCorthals, GarryLogarinho, ElsaMaciel, P.HostingInstitutionOrganizationalRepositóriUM - Universidade do Minhoe-mailmailto:repositorium@usdb.uminho.ptrepositorium@usdb.uminho.ptPMID19545544ISSNIsPartOf0006-291XEISSNIsPartOf1090-2104DOIIsPartOf10.1016/j.bbrc.2009.06.0922009-092009-09-01T00:00:00Z10000-01-01T00:00:00ZHandlehttps://hdl.handle.net/1822/67644http://purl.org/coar/access_right/c_16ecrestricted accessAdaptor proteins, Signal transducingAdenosine triphosphatasesAnimalsAtaxin-3Caenorhabditis elegansCaenorhabditis elegans proteinsCell cycle proteinsMultiprotein complexesNerve tissue proteinsProtein interaction domains and motifsProtein interaction mappingValosin containing proteinPolyglutamineMachado–Joseph diseaseSpinocerebellar ataxia type 3Ubiquitin–proteasome pathwayDeubiquitylating enzyme1550519 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_f1cfapplication/pdffulltexthttps://repositorium.uminho.pt/bitstreams/3e3d8092-0214-4dbe-8045-fcc0906799fc/download |
| spellingShingle | ATX-3, CDC-48 and UBXN-5: a new trimolecular complex in Caenorhabditis elegans Rodrigues, Ana João Adaptor proteins, Signal transducing Adenosine triphosphatases Animals Ataxin-3 Caenorhabditis elegans Caenorhabditis elegans proteins Cell cycle proteins Multiprotein complexes Nerve tissue proteins Protein interaction domains and motifs Protein interaction mapping Valosin containing protein Polyglutamine Machado–Joseph disease Spinocerebellar ataxia type 3 Ubiquitin–proteasome pathway Deubiquitylating enzyme |
| status | SINGLETON |
| subject.fl_str_mv | Adaptor proteins, Signal transducing Adenosine triphosphatases Animals Ataxin-3 Caenorhabditis elegans Caenorhabditis elegans proteins Cell cycle proteins Multiprotein complexes Nerve tissue proteins Protein interaction domains and motifs Protein interaction mapping Valosin containing protein Polyglutamine Machado–Joseph disease Spinocerebellar ataxia type 3 Ubiquitin–proteasome pathway Deubiquitylating enzyme |
| title | ATX-3, CDC-48 and UBXN-5: a new trimolecular complex in Caenorhabditis elegans |
| title_full | ATX-3, CDC-48 and UBXN-5: a new trimolecular complex in Caenorhabditis elegans |
| title_fullStr | ATX-3, CDC-48 and UBXN-5: a new trimolecular complex in Caenorhabditis elegans |
| title_full_unstemmed | ATX-3, CDC-48 and UBXN-5: a new trimolecular complex in Caenorhabditis elegans |
| title_short | ATX-3, CDC-48 and UBXN-5: a new trimolecular complex in Caenorhabditis elegans |
| title_sort | ATX-3, CDC-48 and UBXN-5: a new trimolecular complex in Caenorhabditis elegans |
| topic | Adaptor proteins, Signal transducing Adenosine triphosphatases Animals Ataxin-3 Caenorhabditis elegans Caenorhabditis elegans proteins Cell cycle proteins Multiprotein complexes Nerve tissue proteins Protein interaction domains and motifs Protein interaction mapping Valosin containing protein Polyglutamine Machado–Joseph disease Spinocerebellar ataxia type 3 Ubiquitin–proteasome pathway Deubiquitylating enzyme |
| topic_facet | Adaptor proteins, Signal transducing Adenosine triphosphatases Animals Ataxin-3 Caenorhabditis elegans Caenorhabditis elegans proteins Cell cycle proteins Multiprotein complexes Nerve tissue proteins Protein interaction domains and motifs Protein interaction mapping Valosin containing protein Polyglutamine Machado–Joseph disease Spinocerebellar ataxia type 3 Ubiquitin–proteasome pathway Deubiquitylating enzyme |
| url | https://hdl.handle.net/1822/67644 |
| visible | 1 |