Institute for Research in Immunology and Cancer, Université de Montréal, C.P. 6128 Succursale Centre-Ville, Montréal, QC, Canada, H3C 3J7.
Département de biochimie et médecine moléculaire, Université de Montréal, C.P. 6128 Succursale Centre-Ville, Montréal, QC, Canada, H3C 3J7.
Nat Commun. 2017 Nov 22;8(1):1701. doi: 10.1038/s41467-017-01876-8.
The Polo kinase is a master regulator of mitosis and cytokinesis conserved from yeasts to humans. Polo is composed of an N-term kinase domain (KD) and a C-term polo-box domain (PBD), which regulates its subcellular localizations. The PBD and KD can interact and inhibit each other, and this reciprocal inhibition is relieved when Polo is phosphorylated at its activation loop. How Polo activation and localization are coupled during mitotic entry is unknown. Here we report that PBD binding to the KD masks a nuclear localization signal (NLS). Activating phosphorylation of the KD leads to exposure of the NLS and entry of Polo into the nucleus before nuclear envelope breakdown. Failures of this mechanism result in misregulation of the Cdk1-activating Cdc25 phosphatase and lead to mitotic and developmental defects in Drosophila. These results uncover spatiotemporal mechanisms linking master regulatory enzymes during mitotic entry.
Polo 激酶是一种从酵母到人类都保守的有丝分裂和胞质分裂的主调控因子。Polo 由一个 N 端激酶结构域（KD）和一个 C 端 Polo 框结构域（PBD）组成，它调节 Polo 的亚细胞定位。PBD 和 KD 可以相互作用并抑制彼此，当 Polo 在其激活环上磷酸化时，这种相互抑制被解除。Polo 在有丝分裂进入时的激活和定位是如何偶联的尚不清楚。在这里，我们报告说，PBD 与 KD 的结合掩盖了一个核定位信号（NLS）。KD 的激活磷酸化导致 NLS 的暴露，并在核膜破裂之前将 Polo 导入细胞核。该机制的失败会导致 Cdk1 激活的 Cdc25 磷酸酶的失调，并导致果蝇的有丝分裂和发育缺陷。这些结果揭示了有丝分裂进入过程中主调控酶的时空机制。
