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- W2081103757 abstract "Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disorder characterized by ataxia and selective neuronal cell loss caused by the expansion of a translated CAG repeat encoding a polyglutamine tract in ataxin-7, the SCA7 gene product. To gain insight into ataxin-7 function and to decipher the molecular mechanisms of neurodegeneration in SCA7, a two-hybrid assay was performed to identify ataxin-7 interacting proteins. Herein, we show that ataxin-7 interacts with the ATPase subunit S4 of the proteasomal 19S regulatory complex. The ataxin-7/S4 association is modulated by the length of the polyglutamine tract whereby S4 shows a stronger association with the wild-type allele of ataxin-7. We demonstrate that endogenous ataxin-7 localizes to discrete nuclear foci that also contain additional components of the proteasomal complex. Immunohistochemical analyses suggest alterations either of the distribution or the levels of S4 immunoreactivity in neurons that degenerate in SCA7 brains. Immunoblot analyses demonstrate reduced levels of S4 in SCA7 cerebella without evident alterations in the levels of other proteasome subunits. These results suggest a role for S4 and ubiquitin-mediated proteasomal proteolysis in the molecular pathogenesis of SCA7." @default.
- W2081103757 created "2016-06-24" @default.
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- W2081103757 date "2001-11-01" @default.
- W2081103757 modified "2023-10-17" @default.
- W2081103757 title "Association of ataxin-7 with the proteasome subunit S4 of the 19S regulatory complex" @default.
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- W2081103757 doi "https://doi.org/10.1093/hmg/10.24.2821" @default.
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