title: Regulation of ataxin-1 phosphorylation and its impact on biology.
abstract: Ataxin-1 protein expression is found in the cytoplasm and nucleus of Purkinje cells, the primary site of spinocerebellar ataxia type 1 (SCA1). Phosphorylation at S776 occurs in the cytoplasm and stabilizes the protein through interaction with 14-3-3, allowing it to translocate into the nucleus where disease is initiated. Phosphorylation and stabilization are enhanced when the polyglutamine expansion is present. In this chapter, we present a model of neurodegeneration in SCA1 initiated through phosphorylation at S776 by cAMP-dependent protein kinase (PKA) and enhanced by the presence of the polyglutamine expansion. The biological methods used to uncover SCA1 pathogenesis and phosphorylation at S776 are described.
authors.affiliation: Institute for Translational Neuroscience, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Sarita
authors.initials: S
authors.lastname: Lagalwar
authors.forename: Harry T
authors.initials: HT
authors.lastname: Orr
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism; D000818:Animals; D000067696:Ataxin-1; D000067528:Ataxins; D001695:Biology / Q000379:methods*; D006801:Humans; D016296:Mutagenesis; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000378:metabolism
chemical_list: D048948:14-3-3 Proteins; C000593749:ATXN1 protein, human; D000067696:Ataxin-1; D000067528:Ataxins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D054648:Protein Phosphatase 2