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https://hdl.handle.net/10316/5324
Title: | NEDD8: A new ataxin-3 interactor | Authors: | 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 |
Keywords: | Polyglutamine; Ubiquitin; E3 ligase; Neurodegeneration; MJD/SCA3 | Issue Date: | 2007 | Citation: | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1773:11 (2007) 1619-1627 | Abstract: | 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. | URI: | https://hdl.handle.net/10316/5324 | Rights: | openAccess |
Appears in Collections: | FCTUC Ciências da Vida - Artigos em Revistas Internacionais |
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