title: Nuclear localization of the spinocerebellar ataxia type 7 protein, ataxin-7.
abstract: Spinocerebellar ataxia type 7 (SCA7) belongs to a group of neurological disorders caused by a CAG repeat expansion in the coding region of the associated gene. To gain insight into the pathogenesis of SCA7 and possible functions of ataxin-7, we examined the subcellular localization of ataxin-7 in transfected COS-1 cells using SCA7 cDNA clones with different CAG repeat tract lengths. In addition to a diffuse distribution throughout the nucleus, ataxin-7 associated with the nuclear matrix and the nucleolus. The location of the putative SCA7 nuclear localization sequence (NLS) was confirmed by fusing an ataxin-7 fragment with the normally cytoplasmic protein chicken muscle pyruvate kinase. Mutation of this NLS prevented protein from entering the nucleus. Thus, expanded ataxin-7 may carry out its pathogenic effects in the nucleus by altering a matrix-associated nuclear structure and/or by disrupting nucleolar function.
authors.affiliation: Institute of Human Genetics, University of Minnesota, Minneapolis 55455, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Kaytor
authors.forename: L A
authors.initials: LA
authors.lastname: Duvick
authors.forename: P J
authors.initials: PJ
authors.lastname: Skinner
authors.forename: M D
authors.initials: MD
authors.lastname: Koob
authors.forename: L P
authors.initials: LP
authors.lastname: Ranum
authors.forename: H T
authors.initials: HT
authors.lastname: Orr
mesh_terms: D000818:Animals; D000067719:Ataxin-7; D019556:COS Cells; D005455:Fluorescent Antibody Technique; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D019913:Nuclear Localization Signals / Q000235:genetics; D015530:Nuclear Matrix / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D011770:Pyruvate Kinase / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020754:Spinocerebellar Ataxias / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D025521:Tumor Suppressor Proteins
chemical_list: C000593829:ATXN7 protein, human; D000067719:Ataxin-7; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D011770:Pyruvate Kinase