ASB proteins interact with Cullin5 and Rbx2 to form E3 ubiquitin ligase complexes
ASB proteins interact with Cullin5 and Rbx2 to form E3 ubiquitin ligase complexes
复制标题
DOI：
10.1016/j.febslet.2005.11.016
复制
发表时间：
2005-12-19
期刊：
影响因子：
3.5
通讯作者：
Masuho, Y
中科院分区：
文献类型：
--
作者：
Kohroki, J;Nishiyama, T;Masuho, Y
锚蛋白重复和SOCS盒(ASB)家族由ASB1至ASB18的18个蛋白组成，属于细胞因子信号传导抑制蛋白(SOCS)盒蛋白超家族。最近显示 ASB2 与某个 Cul-Rbx 模块相互作用形成 E3 泛素 (Ub) 连接酶复合物，但包含 ASB 的 E3 Ub 连接酶复合物的功能组成仍有待表征。在这里，我们发现 ASB 蛋白与细胞中的 Cul5-Rbx2 相互作用，但不与 Cul2 或 Rbx1 相互作用。突变分析表明，ASB蛋白SOCS盒中BC盒和Cul5盒高度保守的氨基酸序列对于与Cul5-Rbx2的相互作用至关重要。尽管 ASB 蛋白与 BC 盒和 Cul5 盒的共有序列略有不同，但所有 5 种测试的 ASB 蛋白均与 Cul5-Rbx2 结合。此外，所有三个测试的含有 Cul5-Rbx2 的 ASB 复合物都被发现具有 E3 Ub 连接酶活性。这些发现表明 ASB 家族蛋白与 Cul5-Rbx2 相互作用形成 E3 Ub 连接酶，并通过泛素化介导的途径发挥重要作用。 (c) 2005 年欧洲生化学会联合会。由 Elsevier B.V. 出版。保留所有权利。
The ankyrin repeat and SOCS box (ASB) family is composed of 18 proteins from ASB1 to ASB18 and belongs to the suppressor of cytokine signaling (SOCS) box protein superfamily. ASB2 was recently shown to interact with a certain Cul-Rbx module to form an E3 ubiquitin (Ub) ligase complex, but the functional composition of the ASB-containing E3 Ub ligase complexes remains to be characterized. Here, we show that ASB proteins interact with Cul5-Rbx2 but neither Cul2 nor Rbx1 in cells. Mutational analysis revealed that the highly conserved amino acid sequences of the BC box and Cul5 box in the SOCS box of ASB proteins were essential for the interaction with Cul5-Rbx2. Although ASB proteins show slight divergences from the consensus sequences of the BC box and Cul5 box, all five tested ASB proteins bound to Cul5-Rbx2. Furthermore, all three tested ASB complexes containing Cul5-Rbx2 were found to have E3 Ub ligase activity. These findings suggest that the ASB family proteins interact with Cul5-Rbx2 to form E3 Ub ligases and play significant roles via a ubiquitination-mediated pathway. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.