Gu Haidong, Roizman Bernard
The Marjorie B. Kovler Viral Oncology Laboratories, University of Chicago, 910 East 58th Street, Chicago, IL 60637, USA.
Proc Natl Acad Sci U S A. 2003 Jul 22;100(15):8963-8. doi: 10.1073/pnas.1533420100. Epub 2003 Jul 10.
Infected cell protein 0 (ICP0) of herpes simplex virus 1 expresses two E3 ubiquitin (Ub) ligase activities mapping in the domains encoded by exons 2 and 3, respectively. Site 1 (exon 3) is responsible for the degradation of the E2 Ub-conjugating enzyme cdc34 whereas site 2 (exon 2) is associated with a ring finger and has been shown to mediate the degradation of promyelocytic leukemia (PML) and Sp100 proteins and the dispersal of nuclear domain 10 (ND10). In in vitro assays site 2 polyubiquitylates the E2 enzymes UbcH5a and UbcH6 but not other (e.g., UbcH7) enzymes. In this article, we show that ectopic expression of dominant negative UbcH5a carrying the substitution C85A delayed or blocked the degradation of PML and Sp100 and dispersal of ND10 whereas ectopic expression of wild-type UbcH5a or dominant negative UbcH6 and UbcH7 carrying the substitutions C131A and C86A, respectively, had no effect. These results link the degradation of PML and Sp100 and the dispersal of ND10 to the E3 activities of ICP0 associated with the UbcH5a E2 enzyme.
单纯疱疹病毒1型的感染细胞蛋白0（ICP0）表现出两种E3泛素（Ub）连接酶活性，分别定位于外显子2和外显子3编码的结构域。位点1（外显子3）负责E2泛素结合酶cdc34的降解，而位点2（外显子2）与一个环状结构域相关，并且已被证明可介导早幼粒细胞白血病（PML）和Sp100蛋白的降解以及核结构域10（ND10）的分散。在体外试验中，位点2可使E2酶UbcH5a和UbcH6多聚泛素化，但不能使其他（如UbcH7）酶多聚泛素化。在本文中，我们发现携带C85A替代的显性负性UbcH5a的异位表达延迟或阻断了PML和Sp100的降解以及ND10的分散，而野生型UbcH5a或分别携带C131A和C86A替代的显性负性UbcH6和UbcH7的异位表达则没有影响。这些结果将PML和Sp100的降解以及ND10的分散与与UbcH5a E2酶相关的ICP0的E3活性联系起来。
