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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Identification of a physiological E2 module for the human anaphase-promoting complex
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Identification of a physiological E2 module for the human anaphase-promoting complex

机译:鉴定人类后期促进复合物的生理E2模块

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摘要

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-specif ic 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 UbcHIO are tightly co-regulated in the cell cycle by APC/C-dependent degradation. We conclude that UbcHIO and Ube2S constitute a physiological E2-module for APC/C, the activity of which is required for spindle assembly and cell division.
机译:后期促进复合物(APC / C)的泛素化对于所有真核生物的增殖都是必不可少的。人类APC / C通过组装K11连接的泛素链来促进有丝分裂调节剂的降解,而泛素链的形成是由其E2 UbcH10引发的。在这里,我们将保守的Ube2S识别为人和果蝇APC / C的K11特异性链延长E2。 Ube2S依赖于与APC / C激活剂Cdc20和Cdh1的细胞周期相关的活动。虽然Ube2S的耗竭已经抑制了细胞中的APC / C,但完整的UbcH10 / Ube2S模块的丢失导致APC / C底物的显着稳定,严重的纺锤体缺陷和强烈的有丝分裂延迟。 Ube2S和UbcHIO在细胞周期中受到APC / C依赖性降解的紧密调控。我们得出的结论是,UbcHIO和Ube2S构成了APC / C的生理E2模块,其活动对于纺锤体组装和细胞分裂是必需的。

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  • 作者单位

    Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720;

    Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720;

    Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720 Department of Genome Dynamics, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 Department of Molecular and Cell Biology, University of Connecticut,Storrs, CT 06269;

    Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720;

    Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720 Department of Genome Dynamics, Lawrence Berkeley National Laboratory, Berkeley, CA 94720;

    Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    K11-linked chain; proteasome; ubiquitin;

    机译:K11链蛋白酶体泛素;

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