SUMO-1共价修饰ataxin-3

Covalent Modification of Ataxin-3 by SUMO-1

为了探讨ataxin-3的正常生理功能以及脊髓小脑型共济失调Ⅲ型/马查多-约瑟夫病的发病机理,采用酵母双杂交技术,选择polyQ扩展突变型ataxin-3全长构建诱饵质粒,筛选成人脑cDNA文库,寻找与之相互作用的蛋白质,筛选到互作蛋白smallubiquitin-likemodifier1(SUMO-1).进一步运用免疫共沉淀技术证实,SUMO-1在哺乳动物细胞中共价修饰野生型和polyQ扩展突变型ataxin-3.免疫荧光共定位实验发现,polyQ扩展突变型ataxin-3形成的核内蛋白聚合体与SUMO-1共定位.研究提示,ataxin-3的正常生理功能可能受SUMO-1的调节,SUMO-1可能参与了脊髓小脑型共济失调Ⅲ型/马查多-约瑟夫病的发病机制.

In order to get insight into the biological function of ataxin-3 and the pathogenesis of spinocerebellar ataxia type 3 and Machado-Joseph disease （SCA3/MJD）, a yeast two-hybrid technology was carried out to screen the adult brain cDNA library using the full-length polyglutamine-expanded ataxin-3 as bait. Small ubiquitin-like modifier 1 （SUMO-1） was identified as a novel ataxin-3-interacting protein. Subsequently, co-immunoprecipitation showed that both the wild-type ataxin-3 and the polyglutamine-expanded ataxin-3 were covalently modified by SUMO-1 in SH-SY5Y cell, immunofluorescence showed that the intranuclear aggregates formatted by the polyglutamine-expanded ataxin-3 co-localized with SUMO-1. Taken together, the data suggest that the biological function of ataxin-3 may be regulated by SUMO-1, and that SUMO-1 may participate in the pathogenesis of SCA3/MJD.