Identification of a physiological E2 module for the human anaphase-promoting complex
Identification of a physiological E2 module for the human anaphase-promoting complex
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DOI：
10.1073/pnas.0907887106
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发表时间：
2009-10-27
影响因子：
11.1
通讯作者：
Rape, Michael
中科院分区：
文献类型：
--
作者：
Williamson, Adam;Wickliffe, Katherine E.;Rape, Michael
在所有真核生物中，后期促进复合体（APC/C）的泛素化对增殖至关重要。人类APC/C通过组装k11连接的泛素链来促进有丝分裂调节因子的降解，其形成由E2 UbcH10启动。在这里，我们确定了保守的Ube2S是人类和果蝇APC/C的k11特异性链延长E2。Ube2S的活性依赖于APC/C激活因子Cdc20和Cdh1的细胞周期依赖性关联。虽然Ube2S的缺失已经抑制了细胞中的APC/C，但完整UbcH10/Ube2S模块的缺失导致APC/C底物的急剧稳定，严重的纺锤体缺陷和强烈的有丝分裂延迟。Ube2S和UbcH10在细胞周期中受到APC/ c依赖性降解的密切共同调控。我们得出结论，UbcH10和Ube2S构成APC/C的生理e2模块，其活性是纺锤体组装和细胞分裂所必需的。
Ubiquitination by the anaphase-promoting complex (APC/C) is essential for proliferation in all eukaryotes. The human APC/C promotes the degradation of mitotic regulators by assembling K11-linked ubiquitin chains, the formation of which is initiated by its E2 UbcH10. Here, we identify the conserved Ube2S as a K11-specific chain elongating E2 for human and Drosophila APC/C. Ube2S depends on the cell cycle-dependent association with the APC/C activators Cdc20 and Cdh1 for its activity. While depletion of Ube2S already inhibits APC/C in cells, the loss of the complete UbcH10/Ube2S-module leads to dramatic stabilization of APC/C substrates, severe spindle defects, and a strong mitotic delay. Ube2S and UbcH10 are tightly co-regulated in the cell cycle by APC/C-dependent degradation. We conclude that UbcH10 and Ube2S constitute a physiological E2-module for APC/C, the activity of which is required for spindle assembly and cell division.