Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Nat Commun. 2013;4:2677. doi: 10.1038/ncomms3677.
Mitotic entry and progression require the activation of several mitotic kinases and the proper regulation and localization of several phosphatases. The activity and localization of each of these enzymes is tightly controlled through a series of specific activators, inhibitors and regulatory subunits. Two proteins, Ensa and Arpp-19, were recently identified as specific inhibitors of PP2A-B55 and are critical for allowing full activity of Cdk1/cyclin B and entry into mitosis. Here we show that Bod1, a protein required for proper chromosome alignment at mitosis, shares sequence similarity with Ensa and Arpp-19 and specifically inhibits the kinetochore-associated PP2A-B56 holoenzyme. PP2A-B56 regulates the stability of kinetochore-microtubule attachments by dephosphorylating several kinetochore proteins. Loss of Bod1 changes the balance of phosphorylation at kinetochores, causing defects in kinetochore function. Bod1, Ensa and Arpp-19 define a family of specific PP2A inhibitors that regulate specific PP2A holoenzymes at distinct locations and points in the cell cycle.
有丝分裂的进入和进程需要激活几种有丝分裂激酶，以及对几种磷酸酶进行适当的调节和定位。这些酶的每种活性和定位都是通过一系列特定的激活剂、抑制剂和调节亚基来严格控制的。最近发现两种蛋白质，Ensa 和 Arpp-19，是 PP2A-B55 的特异性抑制剂，对于允许 Cdk1/cyclin B 的完全活性和进入有丝分裂是至关重要的。在这里，我们表明，Bod1 是有丝分裂中正确染色体排列所必需的蛋白质，与 Ensa 和 Arpp-19 具有序列相似性，并且特异性抑制着丝粒相关的 PP2A-B56 全酶。PP2A-B56 通过去磷酸化几种着丝粒蛋白来调节着丝粒微管连接的稳定性。Bod1 的缺失改变了着丝粒的磷酸化平衡，导致着丝粒功能缺陷。Bod1、Ensa 和 Arpp-19 定义了一组特定的 PP2A 抑制剂，它们在细胞周期的不同位置和时间点调节特定的 PP2A 全酶。
