Ubiquitylation of MHC class I by the K3 viral protein signals internalization and TSG101-dependent degradation
Ubiquitylation of MHC class I by the K3 viral protein signals internalization and TSG101-dependent degradation
复制标题
DOI：
10.1093/emboj/21.10.2418
复制
发表时间：
2002-05-15
期刊：
影响因子：
11.4
通讯作者：
Lehner, PJ
中科院分区：
文献类型：
--
作者：
Hewitt, EW;Duncan, L;Lehner, PJ
卡波西肉瘤相关疱疹病毒基因产物K3（KK 3）通过下调来自质膜的MHC I类分子来破坏MHC I类抗原呈递途径。我们现在表明，KK 3协会与MHC I类分子，并促进泛素化的I类出口后，从内质网。泛素化需要KK 3 N-末端植物同源结构域，并提供I类在质膜内化的信号。一旦内化，泛素化的MHC I类被靶向到晚期内吞途径，在那里它被降解。TSG 101（一种参与晚期内体分选的泛素酶2变体蛋白）的小干扰RNA消耗可防止I类降解，并在KK 3表达细胞中保留细胞表面I类表达。这些结果表明，KK 3诱导的I类泛素化提供了一种机制，通过这种机制，内化和分选到晚期内体途径进行降解。KK 3是第一个通过泛素依赖性内体分选机制破坏宿主蛋白运输的病毒基因产物。
The Kaposi's sarcoma-associated herpes virus gene product K3 (KK3) subverts the MHC class I antigen presentation pathway by downregulating MHC class I from the plasma membrane. We now show that KK3 associates with MHC class I molecules and promotes ubiquitylation of class I after export from the endoplasmic reticulum. Ubiquitylation requires the KK3 N-terminal plant homeodomain and provides the signal for class I internalization at the plasma membrane. Once internalized, ubiquitylated MHC class I is targeted to the late endocytic pathway, where it is degraded. Depletion by small interfering RNA of TSG101, a ubiquitin enzyme 2 variant protein involved in late endosomal sorting, prevents class I degradation and preserves cell surface class I expression in KK3-expressing cells. These results suggest a mechanism by which the KK3-induced class I ubiquitylation provides a signal for both internalization and sorting to the late endosomal pathway for degradation. KK3 is the first viral gene product that subverts the trafficking of a host protein via the ubiquitin-dependent endosomal sorting machinery.