Playing polo during mitosis: PLK1 takes the lead

Abstract

Polo-like kinase 1 (PLK1), the prototypical member of the polo-like family of serine/threonine kinases, is a pivotal regulator of mitosis and cytokinesis in eukaryotes. Many layers of regulation have evolved to target PLK1 to different subcellular structures and to its various mitotic substrates in line with its numerous functions during mitosis. Collective work is starting to illuminate an important set of substrates for PLK1: the mitotic kinases that together ensure the fidelity of the cell division process. Amongst these, recent developments argue that PLK1 regulates the activity of the histone kinases Aurora B and Haspin to define centromere identity, of MPS1 to initiate spindle checkpoint signaling, and of BUB1 and its pseudokinase paralog BUBR1 to coordinate spindle checkpoint activation and inactivation. Here, we review the recent work describing the regulation of these kinases by PLK1. We highlight common themes throughout and argue that a major mitotic function of PLK1 is as a master regulator of these key kinases.

Kinetochore phosphatases suppress autonomous kinase activity to control the spindle assembly checkpoint

“…However, if the correct bioriented stated is achieved and the kinetochore comes under tension, then the PP1 arm is engaged 42 , which crucially, is not restricted by negative feedback (Figure 4B). In fact, we speculate that this tension-dependent switch is reinforced by positive feedback instead, because removal of PLK1 and the BUB complex may reduce the inhibitory Aurora B signal emanating from centromeres 19,43 .…”

“…One key unexplained aspect of SAC signalling concerns the role of polo-like kinase 1 (PLK1) 19 . PLK1 interacts via its polo-box domains (PBDs) to phospho-epitopes on various different kinetochore complexes, including to two CDK1 phosphorylation sites on the BUB complex (BUB1-pT609 and BUBR1-pT620) [20][21][22] .…”

Combination Treatment of Polo-Like Kinase 1 and Tankyrase-1 Inhibitors Enhances Anticancer Effect in Triple-negative Breast Cancer Cells

“…The serine/threonine kinase polo-like kinase 1 (PLK1) is known to play an important role in mitosis (5). A striking feature of PLK1 is its localization to numerous subcellular structures during mitosis.…”

FAM 83D directs protein kinase CK 1α to the mitotic spindle for proper spindle positioning

“…The prominent mitotic roles for kinases such as cyclin-dependent kinases (CDKs), Aurora kinases, Polo-like kinases (PLKs) and Nimarelated kinases (NEKs) have been well characterised [1][2][3][4][5][6][7]. However, the role of Casein Kinase 1 alpha (CK1a) in mitosis, if any, remains poorly defined.…”