Implications of specific lysine residues within ataxin-3 for the molecular pathogenesis of Machado-Joseph disease.

ABSTRACT: Lysine residues are one of the main sites for posttranslational modifications of proteins, and lysine ubiquitination of the Machado-Joseph disease protein ataxin-3 is implicated in its cellular function and polyglutamine expansion-dependent toxicity. Despite previously undertaken efforts, the individual roles of specific lysine residues of the ataxin-3 sequence are not entirely understood and demand further analysis. By retaining single lysine residues of otherwise lysine-free wild-type and polyglutamine-expanded ataxin-3, we assessed the effects of a site-limited modifiability on ataxin-3 protein levels, aggregation propensity, localization, and stability. We confirmed earlier findings that levels of lysine-free ataxin-3 are reduced due to its decreased stability, which led to a diminishe

SUBMITTER: Pereira Sena P 

PROVIDER: S-EPMC10235640 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature