Hsp70/Hsc70 regulates the effect phosphorylation has on stabilizing ataxin-1

Nathan D. Jorgensen, J. Michael Andresen, Jason E. Pitt, Melissa A. Swenson, Huda Y. Zoghbi, Harry T. Orr

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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.

Original languageEnglish (US)
Pages (from-to)2040-2048
Number of pages9
JournalJournal of Neurochemistry
Volume102
Issue number6
DOIs
StatePublished - Sep 2007

Keywords

  • ATXN1
  • Ataxin-1
  • Cerebellar ataxia
  • Hsc70
  • Hsp70/Hsc70 Akt
  • Polyglutamine
  • Spinocerebellar ataxia type 1

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    Jorgensen, N. D., Andresen, J. M., Pitt, J. E., Swenson, M. A., Zoghbi, H. Y., & Orr, H. T. (2007). Hsp70/Hsc70 regulates the effect phosphorylation has on stabilizing ataxin-1. Journal of Neurochemistry, 102(6), 2040-2048. https://doi.org/10.1111/j.1471-4159.2007.04678.x