Coupling of Polo kinase activation to nuclear localization by a bifunctional NLS is required during mitotic entry

被引：29

作者：

Kachaner, David ^{[1
,2
]}

Garrido, Damien ^{[1
,2
]}

Mehsen, Haytham ^{[1
]}

Normandin, Karine ^{[1
]}

Lavoie, Hugo ^{[1
]}

Archambault, Vincent ^{[1
,2
]}

机构：

[1] Univ Montreal, Inst Res Immunol & Canc, CP 6128 Succursale Ctr Ville, Montreal, PQ H3C 3J7, Canada

[2] Univ Montreal, Dept Biochim & Med Mol, CP 6128 Succursale Ctr Ville, Montreal, PQ H3C 3J7, Canada

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

基金：

加拿大创新基金会; 加拿大健康研究院; 加拿大自然科学与工程研究理事会;

关键词：

CELL-CYCLE PROGRESSION; PLK1; PHOSPHORYLATION; STRUCTURAL BASIS; PROTEIN-KINASES; SPINDLE POLES; DROSOPHILA; MITOSIS; AURORA; DOMAIN; POLO-LIKE-KINASE-1;

D O I：

10.1038/s41467-017-01876-8

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：16

共 59 条

[1] TWINE, A CDC25 HOMOLOG THAT FUNCTIONS IN THE MALE AND FEMALE GERMLINE OF DROSOPHILA [J].