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

Abstract

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 novel spatiotemporal mechanisms linking master regulatory enzymes during mitotic entry.All rights reserved. No reuse allowed without permission.

Regulating a key mitotic regulator, polo‐like kinase 1 (PLK1)

“…Interestingly, a recent study identified a mechanism for nuclear localization of PLK1 where PBD binding to the kinase domain masks a nuclear localization signal in PLK1. Phosphorylation of the kinase domain within the T‐loop leads to exposure of an NLS causing the entry of PLK1 into the nucleus during G2 (Kachaner et al, ).…”