NEDD8: A new ataxin-3 interactor
| Autor: | Sandra Macedo-Ribeiro, Anabela Ferro, Ricardo J. Tomé, Luísa Cortes, Patrícia Maciel, Elsa Logarinho, Andreia Teixeira-Castro, Ana Luísa Carvalho, A.J. Rodrigues, Carla Malaquias Almeida, Jorge Sequeiros |
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| Přispěvatelé: | [et al.], Universidade do Minho |
| Jazyk: | angličtina |
| Předmět: |
Models
Molecular congenital hereditary and neonatal diseases and abnormalities Binding sites Substrate specificity Plasma protein binding MJD/SCA3 NEDD8 03 medical and health sciences 0302 clinical medicine Nuclear proteins UBL Ubiquitin Nerve tissue proteins medicine Animals Humans Protein binding HeLa cells NEDD8 protein Neurodegeneration Ataxin-3 Ubiquitins Molecular Biology Caenorhabditis elegans E3 ligase 030304 developmental biology Genetics Mammals 0303 health sciences Science & Technology biology Protein transport Two-Hybrid system techniques Hydrolysis Cell Biology biology.organism_classification medicine.disease 3. Good health Cell biology Transport protein Ubiquitin ligase Ataxin biology.protein Repressor proteins Polyglutamine 030217 neurology & neurosurgery |
| Zdroj: | Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP |
| ISSN: | 0167-4889 |
| DOI: | 10.1016/j.bbamcr.2007.07.012 |
| Popis: | 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. We thank Dr. H. Paulson, Dr. R. Hay, Dr. D. Bohmann, Dr. S.Elledge and PM laboratory members for the reagents and as-sistance provided. A.F. would like to address special thanks toCarlos Melo for the continuous support, Maria do Carmo Costaand Sandra Santos for all the assistance with the Y2H and cellculture assays. This work was funded by FCT (POCTI/MGI/47550/2002; SAU-MMO 60412/2004; POCI/SAU-MMO/60156/2004), Fundação Luso-Americana para o Desenvolvi-mento (Proc.3.L/A.II/I P.582/99) and the National Ataxia Foun-dation. A.F. (SFRH/BD/1288/2000), A.T.-C. (SFRH/BI/11844/2003) and A.-J.R. (SFRH/BD/17066/2004) are scholarship re-cipients from FCT. |
| Databáze: | OpenAIRE |
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