Both BC-Box motifs of adenovirus protein E4orf6 are required to efficiently assemble an E3 ligase complex that degrades p53
Both BC-Box motifs of adenovirus protein E4orf6 are required to efficiently assemble an E3 ligase complex that degrades p53
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DOI：
10.1128/mcb.24.21.9619-9629.2004
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发表时间：
2004-11-01
影响因子：
5.3
通讯作者：
Branton, PE
中科院分区：
文献类型：
--
作者：
Blanchette, P;Cheng, CY;Branton, PE
小DNA肿瘤病毒典型地编码蛋白质，该蛋白质使p53降解或降解。人类腺病毒编码的产物，包括E4 orf 6和E1 B55 K，两者都有。每一种都独立地与p53结合并抑制其激活基因表达的能力;然而，它们组合在一起通过泛素途径诱导p53降解。我们先前已经表明，p53降解依赖于E4 orf 6与细胞蛋白Cul 5、Rbx 1以及延伸蛋白B和C的相互作用，以形成类似于SCF和VBC复合物的E3连接酶。在这里，我们表明，像其他elongin BC相互作用蛋白，包括elongin A，von Hippel-Lindau蛋白和Muf 1，E4 orf 6的相互作用是由BC盒基序介导的;然而，E4 orf 6独特地利用两个BC盒基序降解p53和另一个靶点Mre 11。此外，我们的数据表明，E1 B55 K与E4 orf 6的相互作用取决于E4 orf 6形成E3连接酶复合物的能力，并且这种复合物的形成可能是所有E4 orf 6-E1 B55 K功能所必需的。
Small DNA tumor viruses typically encode proteins that either inactivate or degrade p53. Human adenoviruses encode products, including E4orf6 and E1B55K, that do both. Each independently binds to p53 and inhibits its ability to activate gene expression; however, in combination they induce p53 degradation by the ubiquitin pathway. We have shown previously that p53 degradation relies on interactions of E4orf6 with the cellular proteins Cul5, Rbx1, and elongins B and C to form an E3 ligase similar to the SCF and VBC complexes. Here we show that, like other elongin BC-interacting proteins, including elongin A, von Hippel-Lindau protein, and Muf1, the interaction of E4orf6 is mediated by the BC-box motif; however, E4orf6 uniquely utilizes two BC-box motifs for degradation of p53 and another target, Mre11. In addition, our data suggest that the interaction of E1B55K with E4orf6 depends on the ability of E4orf6 to form the E3 ligase complex and that such complex formation may be required for all E4orf6-E1B55K functions.