西亚试剂：调控有丝分裂的磷酸酶小分队

科学家们发现，三个轮番上阵的磷酸酶，组成了一个控制有丝分裂的小分队。

细胞依赖调控系统确保细胞分裂周期的每个步骤以正确的顺序发生。在有丝分裂过程中，细胞会发生大规模的结构重组，这是通过广泛的蛋白磷酸化实现的。蛋白磷酸化受到两种酶的协调控制：负责添加磷酸基团的激酶，和负责去磷酸化的磷酸酶。在基因组成功分离之后，细胞必须通过有丝分裂退出(mitotic exit)恢复分裂前的状态，而磷酸酶活性在这个程序里起到了至关重要的作用。

对于所有多细胞生物来说，有丝分裂退出都是不可逆转的。这一过程出现问题会导致细胞异常生长。实际上，有丝分裂退出的调控失常是癌细胞的一个关键特征。

日前，曼彻斯特大学的研究团队通过研究酵母细胞，揭示了一个控制有丝分裂退出的重要机制。这项研究发表在12月10日的Nature杂志上。

磷酸酶能通过去磷酸改变生物分子的活性，影响分子控制的细胞活动，它们与激酶的作用刚好相反。之前人们曾发现，一些癌症存在着过度的激酶活性。

领导这项研究的Iain Hagan教授说：“我们特别希望了解蛋白磷酸酶PP1、PP 2A-B55和 PP 2A-B56在这一过程中起到了什么作用。”PP1和PP2A承担了人类细胞95%的磷酸酶活性。人们一直认为，这些酶并没有什么关联，功能上也不存在交集。

然而研究人员发现，磷酸酶PP1、PP2A-B55和PP2A-B56是轮番激活的。PP1首先激活PP2A-B55，随后PP2A-B55再去激活PP2A-B56。在这个组合中PP1是主要的调控子，控制着其他两种磷酸酶的活化时间。

研究表明，PP1、PP2A-B55和PP2A-B56组成了一个去磷酸化的小分队，帮助酵母细胞顺利通过有丝分裂的不同阶段。

“这个细胞程序是比较保守的，我们在酵母中的发现，将有助于人们进一步理解人类的细胞分裂，”Hagan教授说。

原文链接：A PP1–PP2A phosphatase relay controls mitotic progression

原文摘要：The widespread reorganization of cellular architecture in mitosis is achieved through extensive protein phosphorylation, driven by the coordinated activation of a mitotic kinase network and repression of counteracting phosphatases. Phosphatase activity must subsequently be restored to promote mitotic exit. Although Cdc14 phosphatase drives this reversal in budding yeast, protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A) activities have each been independently linked to mitotic exit control in other eukaryotes1, 2, 3, 4, 5, 6. Here we describe a mitotic phosphatase relay in which PP1 reactivation is required for the reactivation of both PP2A-B55 and PP2A-B56 to coordinate mitotic progression and exit in fission yeast. The staged recruitment of PP1 (the Dis2 isoform) to the regulatory subunits of the PP2A-B55 and PP2A-B56 (B55 also known as Pab1; B56 also known as Par1) holoenzymes sequentially activates each phosphatase. The pathway is blocked in early mitosis because the Cdk1–cyclin B kinase (Cdk1 also known as Cdc2) inhibits PP1 activity, but declining cyclin B levels later in mitosis permit PP1 to auto-reactivate1, 7, 8, 9, 10. PP1 first reactivates PP2A-B55; this enables PP2A-B55 in turn to promote the reactivation of PP2A-B56 by dephosphorylating a PP1-docking site in PP2A-B56, thereby promoting the recruitment of PP1. PP1 recruitment to human, mitotic PP2A-B56 holoenzymes and the sequences of these conserved PP1-docking motifs11, 12 suggest that PP1 regulates PP2A-B55 and PP2A-B56 activities in a variety of signalling contexts throughout eukaryotes.

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