Department of Genetics, University of Cambridge, Downing Street, Cambridge CB3 9JW, UK.
Open Biol. 2012 Mar;2(3):120023. doi: 10.1098/rsob.120023.
The role of the dual specificity protein phosphatase, Cdc25, in activating the cyclin-dependent kinase-cyclin B complex (Cdk1-CycB) by overcoming the inhibitory Wee1 kinase is a long-established principle for mitotic entry. Recently, however, evidence has emerged of a regulatory network that facilitates Cdk1-CycB activity by inhibiting the form of protein phosphatase 2A having a B55 regulatory subunit (PP2A-B55). Here, I review the genetic and biochemical evidence for Greatwall kinase and its substrate Endosulphine as the key components of this previously obscure regulatory network. Not only is the inhibition of PP2A-B55 by phospho-endosulphine required to prevent dephosphorylation of Cdk1-CycB substrates until mitotic exit, but it is also required to promote Cdc25 activity and inhibit Wee1 at mitotic entry. I discuss how these alternating states of preferential PP2A-B55 or Cdk1-CycB activity can have an impact upon the regulation of Polo kinase and its ability to bind different partner proteins as mitosis progresses.
双重特异性蛋白磷酸酶 Cdc25 通过克服抑制性 Wee1 激酶来激活细胞周期蛋白依赖性激酶-细胞周期蛋白 B 复合物（Cdk1-CycB）的作用，这是有丝分裂进入的一个既定原则。然而，最近有证据表明，通过抑制具有 B55 调节亚基的蛋白磷酸酶 2A 形式（PP2A-B55），可以形成一个调节网络来促进 Cdk1-CycB 的活性。在这里，我回顾了 Greatwall 激酶及其底物 Endosulphine 作为这个以前不为人知的调节网络的关键组成部分的遗传和生化证据。不仅抑制磷酸化的 Endosulphine 对 PP2A-B55 的抑制作用，以防止有丝分裂退出前 Cdk1-CycB 底物的去磷酸化，而且还需要促进 Cdc25 活性和抑制有丝分裂进入时的 Wee1。我讨论了这些优先 PP2A-B55 或 Cdk1-CycB 活性的交替状态如何影响 Polo 激酶的调节及其在有丝分裂过程中结合不同伴侣蛋白的能力。
