IDENTIFICATION OF CLP1P INTERACTING PROTEINS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在真核生物中，退出有丝分裂是通过CDK1-Cyclin B激酶复合体的失活和其磷酸化事件的逆转而发生的。这些晚期有丝分裂事件被严格控制为只发生在后期开始之后和胞质分裂之前。这个调控的中心是保守的蛋白磷酸酶CDC14家族，它的活性逆转了CDK依赖的磷酸化事件。酿酒酵母CDC14的活性受到抑制，使其不能去磷酸化CDK底物，并在后期通过核仁隔离使CDK1失活。在这里，我们描述了一种独特的CDC14调节模式，它在分裂酵母的后期之前运作。CDK1磷酸化并抑制CDC14家族成员CLP1/Flp1的催化活性。当CDK1活性在后期进程中下降时，CLP1/Flp1自动催化逆转这些磷酸化事件来刺激自身的活性。这些发现指出了一个简单的调节电路，它通过依赖磷酸化的CLP1/Flp1磷酸酶活性调节介导CDK1的激活和失活。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In eukaryotes, exit from mitosis occurs through the inactivation of the Cdk1-cyclin B kinase complex and the reversal of its phosphorylation events. These late mitotic events are tightly regulated to occur only after the onset of anaphase and prior to cytokinesis. Central to this regulation is the conserved Cdc14 family of protein phosphatases, whose activity reverses Cdk-dependent phosphorylation events. S. cerevisiae Cdc14 activity is restrained from dephosphorylating Cdk substrates and inactivating Cdk1 through its nucleolar sequestration prior to anaphase. Here, we describe a unique mode of Cdc14 regulation that operates prior to anaphase in fission yeast. Cdk1 phosphorylates and inhibits the catalytic activity of the Cdc14 family member, Clp1/Flp1. As Cdk1 activity declines during anaphase progression, Clp1/Flp1 autocatalytically reverses these phosphorylation events to stimulate its own activity. These findings point to a simple regulatory circuit that couples Cdk1 activation with its inactivation mediated through phosphorylation-dependent regulation of Clp1/Flp1 phosphatase activity.