BTB proteins are substrate-specific adaptors in an SCF-like modular ubiquitin ligase containing CUL-3
BTB proteins are substrate-specific adaptors in an SCF-like modular ubiquitin ligase containing CUL-3
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DOI：
10.1038/nature01985
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发表时间：
2003-09-18
期刊：
影响因子：
64.8
通讯作者：
Harper, JW
中科院分区：
文献类型：
--
作者：
Xu, L;Wei, Y;Harper, JW
通过泛素-蛋白酶体系统对调节蛋白进行程序性破坏是一种广泛使用的控制信号转导通路的机制(1,2)。 Cullins(3) 是作为模块化泛素连接酶支架的蛋白质，以 SCF (Skp1-Cul1-F-box) 复合物 (4-6) 为代表。这些 E3 连接酶的底物选择性由结合 cullin 的特异性模块决定。在 SCF 复合体中，该模块由直接与 Cul1 结合的 Skp1 和 F-box 蛋白家族的成员 (4-7) 组成。 F-box 蛋白通过 F-box 基序 (7) 结合 Skp1，并通过羧基末端蛋白相互作用结构域 (1,2,5) 结合底物。类似地，Cul2 和 Cul5 通过 Skp1 样蛋白 elongin C-2 与含有 BC-box 的特异性因子相互作用。 Cul3 是哺乳动物和秀丽隐杆线虫 (8-10) 胚胎发育所必需的，但其特异性模块尚不清楚。在这里，我们报告了一个大家族的 BTB 结构域蛋白的鉴定，作为线虫 CUL-3 的底物特异性接头。使用 BTB 蛋白 MEL-26 及其遗传靶标 MEI-1（参考文献 12、13）进行的生化研究表明，BTB 蛋白将 Skp1 和 F-box 蛋白的功能特性合并为单个多肽。
Programmed destruction of regulatory proteins through the ubiquitin-proteasome system is a widely used mechanism for controlling signalling pathways(1,2). Cullins(3) are proteins that function as scaffolds for modular ubiquitin ligases typified by the SCF (Skp1-Cul1-F-box) complex(4-6). The substrate selectivity of these E3 ligases is dictated by a specificity module that binds cullins. In the SCF complex, this module is composed of Skp1, which binds directly to Cul1, and a member of the F-box family of proteins(4-7). F-box proteins bind Skp1 through the F-box motif(7), and substrates by means of carboxy-terminal protein interaction domains(1,2,5). Similarly, Cul2 and Cul5 interact with BC-box-containing specificity factors through the Skp1-like protein elongin C-2. Cul3 is required for embryonic development in mammals and Caenorhabditis elegans(8-10) but its specificity module is unknown. Here we report the identification of a large family of BTB-domain proteins as substrate-specific adaptors for C. elegans CUL-3. Biochemical studies using the BTB protein MEL-26 and its genetic target MEI-1 (refs 12, 13) indicate that BTB proteins merge the functional properties of Skp1 and F-box proteins into a single polypeptide.