title: SCA1-phosphorylation, a regulator of Ataxin-1 function and pathogenesis.
abstract: Spinocerebellar ataxia type 1 (SCA1) is one an intriguing set of nine neurodegenerative diseases caused by the expansion of a unstable trinucleotide CAG repeat where the repeat is located within the coding of the affected gene, i.e. the polyglutamine (polyQ) diseases. A gain-of-function mechanism for toxicity in SCA1, like the other polyQ diseases, is thought to have a major role in pathogenesis. Yet, the specific nature of this gain-of-function is a matter of considerable discussion. An issue concerns whether toxicity stems from the native or normal function of the affected protein versus a novel function induced by polyQ expansion. For SCA1 considerable evidence is accumulating that pathology is mediated by a polyQ-induced exaggeration of a native function of the host protein Ataxin-1 (ATXN1) and that phosphorylation of S776 regulates its interaction with other cellular protein and thereby function. In addition, this posttranslational modification modulates toxicity of ATXN1 with an expanded polyglutamine.
authors.affiliation: Institute for Translational Neuroscience, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA. orrxx002@umn.edu
authors.forename: Harry T
authors.initials: HT
authors.lastname: Orr
mesh_terms: D000818:Animals; D000067696:Ataxin-1; D000067528:Ataxins; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D011689:Purkinje Cells / Q000378:metabolism / Q000473:pathology; D020754:Spinocerebellar Ataxias / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: C000593749:ATXN1 protein, human; D000067696:Ataxin-1; D000067528:Ataxins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; C097188:polyglutamine