title: SUMOylation of the polyglutamine repeat protein, ataxin-1, is dependent on a functional nuclear localization signal.
abstract: SUMO (small ubiquitin-like modifier) is a member of the ubiquitin family of proteins. SUMO targets include proteins involved in numerous roles including nuclear transport and transcriptional regulation. The previous finding that mutant ataxin-1[82Q] disrupted promyelocytic leukemia (PML) oncogenic domains prompted us to determine whether ataxin-1 disrupts another component of PML oncogenic domains, Sp100 (100-kDa Speckled protein). Similar to the PML protein, mutant ataxin-1[82Q] redistributed Sp100 to mutant ataxin-1[82Q] nuclear inclusions. Based on the ability of PML and Sp100 to be covalently modified by SUMO, we investigated the ability of ataxin-1 to be SUMOylated. SUMO-1 was found to covalently modify the polyglutamine repeat protein ataxin-1. There was a decrease in ataxin-1 SUMOylation in the presence of the expanded polyglutamine tract, ataxin-1[82Q]. The phospho-mutant, ataxin-1[82Q]-S776A, restored SUMO levels to those of wild-type ataxin-1[30Q]. SUMOylation of ataxin-1 was dependent on a functional nuclear localization signal. Ataxin-1 SUMOylation was mapped to at least five lysine residues. Lys(16), Lys(194) preceding the polyglutamine tract, Lys(610)/Lys(697) in the C-terminal ataxin high mobility group domain, and Lys(746) all contribute to ataxin-1 SUMOylation.
authors.affiliation: Department of Biochemistry, Molecular Biology, Biophysics, Institute of Human Genetics, The University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Brigit E
authors.initials: BE
authors.lastname: Riley
authors.forename: Huda Y
authors.initials: HY
authors.lastname: Zoghbi
authors.forename: Harry T
authors.initials: HT
authors.lastname: Orr
mesh_terms: D021581:Active Transport, Cell Nucleus; D020816:Amino Acid Motifs; D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D000067696:Ataxin-1; D000067528:Ataxins; D001324:Autoantigens / Q000378:metabolism; D001665:Binding Sites; D019556:COS Cells; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D003902:Detergents / Q000494:pharmacology; D047468:Immunoprecipitation; D008239:Lysine / Q000737:chemistry; D008856:Microscopy, Fluorescence; D009363:Neoplasm Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D017830:Octoxynol / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D025521:Tumor Suppressor Proteins
chemical_list: C000593749:ATXN1 protein, human; D034961:Antigens, Nuclear; D000067696:Ataxin-1; D000067528:Ataxins; D001324:Autoantigens; D003902:Detergents; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; D010455:Peptides; D025841:Small Ubiquitin-Related Modifier Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C066642:SP100 protein, human; C097188:polyglutamine; D017830:Octoxynol; D008239:Lysine