SUMO-1 Modification on K166 of PolyQ-Expanded aTaxin-3 Strengthens Its Stability and Increases Its Cytotoxicity

Post-translational modification by SUMO was proposed to modulate the pathogenesis of several neurodegenerative diseases. Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is an autosomal dominant neurodegenerative disease caused by polyQ-expanded ataxin-3. We have previously shown that...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhou, Ya-Fang, Liao, Shu-Sheng, Luo, Ying-Ying, Tang, Jian-Guang, Wang, Jun-Ling, Lei, Li-Fang, Chi, Jing-Wei, Du, Juan, Jiang, Hong, Xia, Kun, Tang, Bei-Sha, Shen, Lu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3561348/
https://www.ncbi.nlm.nih.gov/pubmed/23382880
http://dx.doi.org/10.1371/journal.pone.0054214
Descripción
Sumario:Post-translational modification by SUMO was proposed to modulate the pathogenesis of several neurodegenerative diseases. Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is an autosomal dominant neurodegenerative disease caused by polyQ-expanded ataxin-3. We have previously shown that ataxin-3 was a new target of SUMOylation in vitro and in vivo. Here we identified that the major SUMO-1 binding site was located on lysine 166. SUMOylation did not influence the subcellular localization, ubiquitination or aggregates formation of mutant-type ataxin-3, but partially increased its stability and the cell apoptosis. Our findings revealed the role of ataxin-3 SUMOylation in SCA3/MJD pathogenesis.

Ejemplares similares