title: Hsp70/Hsc70 regulates the effect phosphorylation has on stabilizing ataxin-1.
abstract: Spinocerebellar ataxia type 1 (SCA1) is an inherited neurodegenerative disorder. The mutation causing SCA1 is an expansion in the polyglutamine tract of the ATXN1 protein. Previous work demonstrated that phosphorylation of mutant ATXN1 at serine 776 (S776), a putative Akt phosphorylation site, is critical for pathogenesis. To examine this pathway further, we utilized a cell-transfection system that allowed the targeting of Akt to either the cytoplasm or the nucleus. In contrast to HeLa cells, we found that Akt targeted to the cytoplasm increased the degradation of ATXN1 in Chinese hamster ovary cells. However, Akt targeted to the cytoplasm failed to destabilize ATXN1 if Hsp70/Hsc70 was present. Thus, Hsp70/Hsc70 can regulate ATXN1 levels in concert with phosphorylation of ATXN1 at S776.
authors.affiliation: Graduate Program in Neuroscience, University of Minnesota, Minneapolis, Minnesota, USAInstitute of Human Genetics, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USAHoward Hughes Medical Institute, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Jorgensen
authors.affiliation: Graduate Program in Neuroscience, University of Minnesota, Minneapolis, Minnesota, USAInstitute of Human Genetics, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USAHoward Hughes Medical Institute, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Andresen
authors.affiliation: Graduate Program in Neuroscience, University of Minnesota, Minneapolis, Minnesota, USAInstitute of Human Genetics, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USAHoward Hughes Medical Institute, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Jason E
authors.initials: JE
authors.lastname: Pitt
authors.affiliation: Graduate Program in Neuroscience, University of Minnesota, Minneapolis, Minnesota, USAInstitute of Human Genetics, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USAHoward Hughes Medical Institute, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Swenson
authors.affiliation: Graduate Program in Neuroscience, University of Minnesota, Minneapolis, Minnesota, USAInstitute of Human Genetics, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USAHoward Hughes Medical Institute, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Huda Y
authors.initials: HY
authors.lastname: Zoghbi
authors.affiliation: Graduate Program in Neuroscience, University of Minnesota, Minneapolis, Minnesota, USAInstitute of Human Genetics, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USAHoward Hughes Medical Institute, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Harry T
authors.initials: HT
authors.lastname: Orr
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000235:genetics; D000818:Animals; D000067696:Ataxin-1; D000067528:Ataxins; D016466:CHO Cells; D002451:Cell Compartmentation / Q000235:genetics; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002525:Cerebellar Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006224:Cricetinae; D003412:Cricetulus; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D011689:Purkinje Cells / Q000378:metabolism* / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020754:Spinocerebellar Ataxias / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D014162:Transfection / Q000379:methods
chemical_list: C000593749:ATXN1 protein, human; D000067696:Ataxin-1; D000067528:Ataxins; C000593750:Atxn1 protein, mouse; D018840:HSP70 Heat-Shock Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D051057:Proto-Oncogene Proteins c-akt