Saposin C抑制雄激素受体的多泛素化以及在蛋白酶体中的降解(英文)  

Down-regulation of the Androgen Receptor Ubiquitination and Degradation by Saposin C in LNCaP cells

作　　者：任凯[1] 任立刚[1] 丁岩[2] 张雅利[2] 

机构地区：[1]西安医学院生物化学教研室,西安710021 [2]西安交通大学生命科学与技术学院,西安710049

出　　处：《中国生物化学与分子生物学报》2014年第5期462-467,共6页Chinese Journal of Biochemistry and Molecular Biology

基　　金：Supported by National Natural Science Foundation of China(No.31101266);Scientific Research Program Funded by Education Department of Shaanxi Province(No.12JK0711)~~

摘　　要：本研究旨在证实鞘脂活化蛋白C(saposin C)对雄激素受体(AR)多泛素化降解的影响及其机制.通过将真核表达载体saposin C转染LNCaP细胞,发现saposin C上调AR的蛋白水平和转录激活活性.进一步将野生型和突变型泛素质粒Ubwt和UbK48R分别与saposin C共转染LNCaP细胞发现,saposin C能够促进AR蛋白的单泛素化形式的稳定性,抑制AR的多泛素化修饰及其在蛋白酶体中的降解.其分子机制是saposin C、Ub和AR三者形成复合体,抑制了AR的进一步多泛素化过程.同时还发现,在这一机制中,细胞内低浓度的雄激素(0.1 nmol/L)与saposin C具有协同作用.In this article we investigated the effect of saposin C on ubiquitination and degradation of androgen receptor （AR） in LNCaP cells. After transient transfections of the eukaryotic expression vectors expressing saposin C, Ubwt or UbK48R into LNCaP cells, Western blot assay was employed to investigate the effect of saposin C on AR protein levels, ubiquitination and degradation. Immunoprecipitation assay was used to investigate the interactions among saposin C, Ub （ubiquitin） and AR. Our results show that saposin C up-regulates the AR protein levels and transactivation activity. Intriguingly, it is found that saposin C strengthens the stability and function of AR protein through the formation of saposin C, Ub and AR complex which restrains the poly- ubiquitination and degradation of the AR in UPS （ubiquitin-proteasome system）. Moreover, saposin C and low concentration androgens cooperatively enhance the inhibition of poly-ubiquitination and degradation of AR.

关 键 词：鞘脂活化蛋白C 雄激素受体 泛素一蛋白酶体系统 前列腺癌 

分 类 号：R737.25[医药卫生—肿瘤]