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MJD is caused by a CAG trinucleotide expansion in the\n                    <jats:italic>ATXN3<\/jats:italic>\n                    gene, which encodes a protein named ataxin\u20103. Ataxin\u20103 has been proposed to act as a deubiquitinating enzyme in the ubiquitin\u2010proteasome 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\u20103, we have identified the\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    orthologue of the\n                    <jats:italic>ATXN3<\/jats:italic>\n                    gene and characterized its pattern of expression, developmental regulation, and subcellular localization. We demonstrate that, analogous to its human orthologue,\n                    <jats:italic>C. elegans<\/jats:italic>\n                    ataxin\u20103 has deubiquitinating activity\n                    <jats:italic>in vitro<\/jats:italic>\n                    against polyubiquitin chains with four or more ubiquitins, the minimum ubiquitin length for proteasomal targeting. To further evaluate\n                    <jats:italic>C. elegans<\/jats:italic>\n                    ataxin\u20103, we characterized the first known knockout animal models both phenotypically and biochemically, and found that the two\n                    <jats:italic>C. elegans<\/jats:italic>\n                    strains were viable and displayed no gross phenotype. To identify a molecular phenotype, we performed a large\u2010scale microarray analysis of gene expression in both knockout strains. The data revealed a significant deregulation of core sets of genes involved in the ubiquitin\u2010proteasome pathway, structure\/motility, and signal transduction. This gene identification provides important clues that can help elucidate the specific biological role of ataxin\u20103 and unveil some of the physiological effects caused by its absence or diminished function.\u2014Rodrigues, A\u2010J., Coppola, G., Santos, C., do Carmo Costa, M., Ailion, M., Sequeiros, J., Geschwind, D. H., Maciel, P. Functional genomics and biochemical characterization of the\n                    <jats:italic>C. elegans<\/jats:italic>\n                    orthologue of the Machado\u2010Joseph disease protein ataxin\u20103.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    21, 1126\u20131136 (2007)\n                  <\/jats:p>","DOI":"10.1096\/fj.06-7002com","type":"journal-article","created":{"date-parts":[[2007,1,18]],"date-time":"2007-01-18T20:48:35Z","timestamp":1169153315000},"page":"1126-1136","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Functional genomics and biochemical characterization of the\n                    <i>C. elegans<\/i>\n                    orthologue of the Machado\u2010Joseph disease protein ataxin\u20103"],"prefix":"10.1096","volume":"21","author":[{"given":"Ana-Jo\u00e3o","family":"Rodrigues","sequence":"first","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS) School of Health Sciences University of Minho Braga Portugal"},{"name":"Program in Neurogenetics Department of Neurology David Geffen School of Medicine-UCLA Los Angeles USA"}]},{"given":"Giovanni","family":"Coppola","sequence":"additional","affiliation":[{"name":"Program in Neurogenetics Department of Neurology David Geffen School of Medicine-UCLA Los Angeles USA"}]},{"given":"Cl\u00e1udia","family":"Santos","sequence":"additional","affiliation":[{"name":"UnlGENe Institute for Molecular and Cell Biology Porto Portugal"}]},{"given":"Maria do Carmo","family":"Costa","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS) School of Health Sciences University of Minho Braga Portugal"}]},{"given":"Michael","family":"Ailion","sequence":"additional","affiliation":[{"name":"Department of Biology University of Utah Salt Lake City Utah USA"}]},{"given":"Jorge","family":"Sequeiros","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS) School of Health Sciences University of Minho Braga Portugal"}]},{"given":"Daniel H.","family":"Geschwind","sequence":"additional","affiliation":[{"name":"Program in Neurogenetics Department of Neurology David Geffen School of Medicine-UCLA Los Angeles USA"}]},{"given":"Patr\u00edcia","family":"Mariel","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS) School of Health Sciences University of Minho Braga Portugal"}]}],"member":"311","published-online":{"date-parts":[[2007,1,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.28.7.703"},{"key":"e_1_2_7_3_1","first-page":"33","article-title":"Joseph's disease: an autosomal dominant neurological disease in the Portuguese of the United States and the Azores Islands","volume":"21","author":"Rosenberg R. 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