Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK.
Science. 2010 Dec 17;330(6011):1670-3. doi: 10.1126/science.1195689.
Entry into mitosis in eukaryotes requires the activity of cyclin-dependent kinase 1 (Cdk1). Cdk1 is opposed by protein phosphatases in two ways: They inhibit activation of Cdk1 by dephosphorylating the protein kinases Wee1 and Myt1 and the protein phosphatase Cdc25 (key regulators of Cdk1), and they also antagonize Cdk1's own phosphorylation of downstream targets. A particular form of protein phosphatase 2A (PP2A) containing a B55δ subunit (PP2A- B55δ) is the major protein phosphatase that acts on model CDK substrates in Xenopus egg extracts and has antimitotic activity. The activity of PP2A-B55δ is high in interphase and low in mitosis, exactly opposite that of Cdk1. We report that inhibition of PP2A-B55δ results from a small protein, known as α-endosulfine (Ensa), that is phosphorylated in mitosis by the protein kinase Greatwall (Gwl). This converts Ensa into a potent and specific inhibitor of PP2A-B55δ. This pathway represents a previously unknown element in the control of mitosis.
真核生物进入有丝分裂需要细胞周期蛋白依赖性激酶 1（Cdk1）的活性。蛋白磷酸酶通过两种方式拮抗 Cdk1：它们通过去磷酸化蛋白激酶 Wee1 和 Myt1 以及蛋白磷酸酶 Cdc25（Cdk1 的关键调节剂）来抑制 Cdk1 的激活，并且它们还拮抗 Cdk1 自身对下游靶标的磷酸化。含有 B55δ 亚基的特定形式的蛋白磷酸酶 2A（PP2A）（PP2A-B55δ）是在爪蟾卵提取物中作用于模型 CDK 底物的主要蛋白磷酸酶，具有抗有丝分裂活性。PP2A-B55δ 的活性在间期高，在有丝分裂中低，与 Cdk1 正好相反。我们报告说，PP2A-B55δ 的抑制作用来自一种称为α-内磺素（Ensa）的小蛋白，它在有丝分裂中被蛋白激酶 Greatwall（Gwl）磷酸化。这将 Ensa 转化为 PP2A-B55δ 的有效且特异性抑制剂。该途径代表了有丝分裂控制中以前未知的元素。
