Di Fiore Barbara, Pines Jonathon
Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, England, UK.
J Cell Biol. 2007 May 7;177(3):425-37. doi: 10.1083/jcb.200611166.
Ubiquitin-mediated proteolysis is critical for the alternation between DNA replication and mitosis and for the key regulatory events in mitosis. The anaphase-promoting complex/cyclosome (APC/C) is a conserved ubiquitin ligase that has a fundamental role in regulating mitosis and the cell cycle in all eukaryotes. In vertebrate cells, early mitotic inhibitor 1 (Emi1) has been proposed as an important APC/C inhibitor whose destruction may trigger activation of the APC/C at mitosis. However, in this study, we show that the degradation of Emi1 is not required to activate the APC/C in mitosis. Instead, we uncover a key role for Emi1 in inhibiting the APC/C in interphase to stabilize the mitotic cyclins and geminin to promote mitosis and prevent rereplication. Thus, Emi1 plays a crucial role in the cell cycle to couple DNA replication with mitosis, and our results also question the current view that the APC/C has to be inactivated to allow DNA replication.
泛素介导的蛋白水解对于DNA复制与有丝分裂之间的转换以及有丝分裂中的关键调控事件至关重要。后期促进复合物/细胞周期体（APC/C）是一种保守的泛素连接酶，在所有真核生物中对调控有丝分裂和细胞周期起着基本作用。在脊椎动物细胞中，早有研究提出早期有丝分裂抑制剂1（Emi1）是一种重要的APC/C抑制剂，其降解可能在有丝分裂时触发APC/C的激活。然而，在本研究中，我们表明Emi1的降解并非有丝分裂时激活APC/C所必需。相反，我们发现Emi1在间期抑制APC/C以稳定有丝分裂周期蛋白和geminin从而促进有丝分裂并防止再复制方面起着关键作用。因此，Emi1在细胞周期中对于将DNA复制与有丝分裂联系起来起着至关重要的作用，并且我们的结果也对目前认为必须使APC/C失活才能进行DNA复制的观点提出了质疑。
