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Hsp70/Hsc70 regulates the effect phosphorylation has on stabilizing ataxin‐1
Author(s) -
Jorgensen Nathan D.,
Andresen J. Michael,
Pitt Jason E.,
Swenson Melissa A.,
Zoghbi Huda Y.,
Orr Harry T.
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04678.x
Subject(s) - phosphorylation , protein kinase b , cytoplasm , microbiology and biotechnology , biology , polyglutamine tract , spinocerebellar ataxia , chinese hamster ovary cell , transfection , pi3k/akt/mtor pathway , mutant , signal transduction , cell culture , biochemistry , gene , genetics , huntingtin
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.