Rbx1, a component of the VHL tumor suppressor complex and SCF ubiquitin ligase
Rbx1, a component of the VHL tumor suppressor complex and SCF ubiquitin ligase
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DOI：
10.1126/science.284.5414.657
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发表时间：
1999-04-23
期刊：
影响因子：
56.9
通讯作者：
Conway, JW
中科院分区：
文献类型：
--
作者：
Kamura, T;Koepp, DM;Conway, JW
von Hippel-Lindau（VHL）肿瘤抑制基因在大多数人肾癌中发生突变。VHL蛋白是复合物的一部分，该复合物包括延伸蛋白B、延伸蛋白C和Cullin-2，这些蛋白与转录延伸和泛素化相关。在这里，它表明，在大鼠肝脏中的内源性VHL复合物还包括Rbx 1，一种进化上保守的蛋白质，含有一个RING-H2指状基序，并与Cullin相互作用。Rbx 1的酵母同源物是含Cdc 53的SCFCdc 4泛素连接酶的亚基和有效激活剂，所述泛素连接酶是细胞周期蛋白依赖性激酶抑制剂Sic 1的泛素化和G（1）到S细胞周期转变所需的。这些发现提供了VHL和细胞泛素化机制之间的进一步联系。
The von Hippel-Lindau (VHL) tumor suppressor gene is mutated in most human kidney cancers. The VHL protein is part of a complex that includes Elongin B, Elongin C, and Cullin-2, proteins associated with transcriptional elongation and ubiquitination. Here it is shown that the endogenous VHL complex in rat liver also includes Rbx1, an evolutionarily conserved protein that contains a RING-H2 fingerlike motif and that interacts with Cullins. The yeast homolog of Rbx1 is a subunit and potent activator of the Cdc53-containing SCFCdc4 ubiquitin ligase required for ubiquitination of the cyclin-dependent kinase inhibitor Sic1 and for the G(1) to S cell cycle transition. These findings provide a further Link between VHL and the cellular ubiquitination machinery.