Fu Zheng, Malureanu Liviu, Huang Jun, Wang Wei, Li Hao, van Deursen Jan M, Tindall Donald J, Chen Junjie
Department of Urology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Nat Cell Biol. 2008 Sep;10(9):1076-82. doi: 10.1038/ncb1767.
Proper control of entry into and progression through mitosis is essential for normal cell proliferation and the maintenance of genome stability. The mammalian mitotic kinase Polo-like kinase 1 (Plk1) is involved in multiple stages of mitosis5. Here we report that Forkhead Box M1 (FoxM1), a substrate of Plk1, controls a transcriptional programme that mediates Plk1-dependent regulation of cell-cycle progression. The carboxy-terminal domain of FoxM1 binds Plk1, and phosphorylation of two key residues in this domain by Cdk1 is essential for Plk1-FoxM1 interaction. Formation of the Plk1-FoxM1 complex allows for direct phosphorylation of FoxM1 by Plk1 at G2/M and the subsequent activation of FoxM1 activity, which is required for expression of key mitotic regulators, including Plk1 itself. Thus, Plk1-dependent regulation of FoxM1 activity provides a positive-feedback loop ensuring tight regulation of transcriptional networks essential for orderly mitotic progression.
对有丝分裂的进入和进程进行适当控制对于正常细胞增殖和基因组稳定性的维持至关重要。哺乳动物有丝分裂激酶Polo样激酶1（Plk1）参与有丝分裂的多个阶段。在此，我们报告Plk1的底物叉头框M1（FoxM1）控制着一个转录程序，该程序介导Plk1依赖的细胞周期进程调控。FoxM1的羧基末端结构域与Plk1结合，Cdk1对该结构域中两个关键残基的磷酸化对于Plk1 - FoxM1相互作用至关重要。Plk1 - FoxM1复合物的形成使得Plk1在G2/M期直接磷酸化FoxM1，并随后激活FoxM1活性，这是包括Plk1自身在内的关键有丝分裂调节因子表达所必需的。因此，Plk1依赖的FoxM1活性调节提供了一个正反馈回路，确保对有序有丝分裂进程所必需的转录网络进行严格调控。
