Di Fiore Barbara, Pines Jonathon
Wellcome Trust/Cancer Research UK Gurdon Institute of Cancer and Developmental Biology, University of Cambridge, Cambridge, UK.
Chromosoma. 2008 Aug;117(4):333-8. doi: 10.1007/s00412-008-0152-x. Epub 2008 Mar 4.
Ordered progression through the cell cycle is essential to maintain genomic stability, and fundamental to this is ubiquitin-mediated proteolysis. In particular, the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase destabilises specific regulators at defined times in the cycle to ensure that each round of DNA replication is followed by cell division. Thus, the proper regulation of the APC/C is crucial in each cell cycle. There are several APC/C regulators that restrict its activity to specific cell cycle phases, and amongst these the early mitotic inhibitor 1 (Emi1) protein has recently come to prominence. Emi1 has been proposed to control APC/C in early mitosis; however, recent evidence questions this role. In this review we discuss new evidence that indicates that Emi1 is essential to restrict APC/C activity in interphase and, by doing so, ensure the proper coordination between DNA replication and mitosis.
细胞周期的有序进行对于维持基因组稳定性至关重要,而泛素介导的蛋白水解作用是其根本所在。特别是,后期促进复合物/细胞周期体(APC/C)泛素连接酶在细胞周期的特定时间使特定调节因子不稳定,以确保每一轮DNA复制后都紧接着进行细胞分裂。因此,APC/C的正确调节在每个细胞周期中都至关重要。有几种APC/C调节因子将其活性限制在特定的细胞周期阶段,其中早期有丝分裂抑制剂1(Emi1)蛋白最近备受关注。有人提出Emi1在有丝分裂早期控制APC/C;然而,最近的证据对这一作用提出了质疑。在这篇综述中,我们讨论了新的证据,这些证据表明Emi1对于在间期限制APC/C活性至关重要,并且通过这样做,确保DNA复制和有丝分裂之间的适当协调。