Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/67807

TitleFunctional genomics and biochemical characterization of the C. elegans orthologue of the Machado-Joseph disease protein ataxin-3
Author(s)Rodrigues, Ana João
Coppola, Giovanni
Santos, Cláudia
Costa, Maria do Carmo
Ailion, Michael
Sequeiros, Jorge
Geschwind, Daniel H.
Maciel, P.
KeywordsAmino acid sequence
Animals
Animals, Genetically modified
Ataxin-3
Caenorhabditis elegans
Caenorhabditis elegans proteins
Cloning, Molecular
Humans
Machado-Joseph disease
Molecular sequence data
Nerve tissue proteins
Peptides
Proteasome endopeptidase complex
Sequence homology, Amino acid
Signal transduction
Ubiquitin
Genomics
Polyglutamine disorders
Ubiquitin-proteasome pathway
Microarray
Ataxia
Knockout
Issue dateApr-2007
PublisherWiley
JournalFaseb Journal
Abstract(s)Machado-Joseph disease (MJD) is the most common dominant spinocerebellar ataxia. MJD is caused by a CAG trinucleotide expansion in the ATXN3 gene, which encodes a protein named ataxin-3. Ataxin-3 has been proposed to act as a deubiquitinating enzyme in the ubiquitin-proteasome pathway and to be involved in transcriptional repression; nevertheless, its precise biological function(s) remains unknown. To gain further insight into the function of ataxin-3, we have identified the Caenorhabditis elegans orthologue of the ATXN3 gene and characterized its pattern of expression, developmental regulation, and subcellular localization. We demonstrate that, analogous to its human orthologue, C. elegans ataxin-3 has deubiquitinating activity in vitro against polyubiquitin chains with four or more ubiquitins, the minimum ubiquitin length for proteasomal targeting. To further evaluate C. elegans ataxin-3, we characterized the first known knockout animal models both phenotypically and biochemically, and found that the two C. elegans strains were viable and displayed no gross phenotype. To identify a molecular phenotype, we performed a large-scale microarray analysis of gene expression in both knockout strains. The data revealed a significant deregulation of core sets of genes involved in the ubiquitin-proteasome pathway, structure/motility, and signal transduction. This gene identification provides important clues that can help elucidate the specific biological role of ataxin-3 and unveil some of the physiological effects caused by its absence or diminished function.
TypeArticle
URIhttp://hdl.handle.net/1822/67807
DOI10.1096/fj.06-7002com
ISSN0892-6638
e-ISSN1530-6860
Peer-Reviewedyes
AccessRestricted access (UMinho)
Appears in Collections:ICVS - Artigos em revistas internacionais / Papers in international journals

Files in This Item:
File Description SizeFormat 
Rodrigues-2007-Functional-genomics-and-biochemical.pdf
  Restricted access
524,82 kBAdobe PDFView/Open

Partilhe no FacebookPartilhe no TwitterPartilhe no DeliciousPartilhe no LinkedInPartilhe no DiggAdicionar ao Google BookmarksPartilhe no MySpacePartilhe no Orkut
Exporte no formato BibTex mendeley Exporte no formato Endnote Adicione ao seu ORCID