NEDD8: a new ataxin-3 interactor.
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.
Mesh Terms:
Animals, Binding Sites, HeLa Cells, Humans, Hydrolysis, Mammals, Models, Molecular, Nerve Tissue Proteins, Nuclear Proteins, Protein Binding, Protein Transport, Repressor Proteins, Substrate Specificity, Two-Hybrid System Techniques, Ubiquitin, Ubiquitins
Animals, Binding Sites, HeLa Cells, Humans, Hydrolysis, Mammals, Models, Molecular, Nerve Tissue Proteins, Nuclear Proteins, Protein Binding, Protein Transport, Repressor Proteins, Substrate Specificity, Two-Hybrid System Techniques, Ubiquitin, Ubiquitins
Biochim. Biophys. Acta
Date: Nov. 01, 2007
PubMed ID: 17935801
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