Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/67703

TitleNEDD8: a new ataxin-3 interactor
Author(s)Ferro, Anabela
Carvalho, Ana Luísa
Castro, Andreia Cristiana Teixeira
Almeida, Carla
Tomé, Ricardo J.
Cortes, Luísa
Rodrigues, Ana João
Santos, Elsa Clara Carvalho Logarinho
Sequeiros, Jorge
Maciel, P.
KeywordsAnimals
Ataxin-3
Binding sites
HeLa cells
Humans
Hydrolysis
Mammals
Models, Molecular
NEDD8 protein
Nerve tissue proteins
Nuclear proteins
Protein binding
Protein transport
Repressor proteins
Substrate specificity
Two-Hybrid system techniques
Ubiquitin
Polyglutamine
UBL
E3 ligase
Neurodegeneration
MJD/SCA3
Issue dateNov-2007
PublisherElsevier
JournalBiochimica et Biophysica Acta (BBA). Molecular Cell Research
Abstract(s)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.
TypeArticle
URIhttp://hdl.handle.net/1822/67703
DOI10.1016/j.bbamcr.2007.07.012
ISSN0167-4889
e-ISSN1879-2596
Publisher versionhttps://www.sciencedirect.com/science/article/pii/S0167488907001917
Peer-Reviewedyes
AccessOpen access
Appears in Collections:ICVS - Artigos em revistas internacionais / Papers in international journals

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