Polo on the Rise—from Mitotic Entry to Cytokinesis with Plk1

Abstract

Polo-like kinase 1 (Plk1) is a key regulator of cell division in eukaryotic cells. New techniques, including the application of small-molecule inhibitors, have greatly expanded our knowledge of the functions, targets, and regulation of this key mitotic enzyme. In this review, we focus on how Plk1 is recruited to centrosomes, kinetochores, and the spindle midzone and what the specific tasks of Plk1 at these distinct subcellular structures might be. In particular, we highlight new work on the role of Plk1 in cytokinesis in human cells. Finally, we describe how better understanding of Plk1 functions allows critical evaluation of Plk1 as a potential drug target for cancer therapy.

Cytokinesis arrest and multiple centrosomes in B cell chronic lymphocytic leukaemia

“…When we performed immunofluorescence staining for Plk1 and Aurora B, proteins known to regulate cytokinesis,11, 12 we found that Plk1 localized at the cytokinesis contractile ring in CLL doublets (Figure 1C), which is a hallmark of cytokinesis 11. Taken together, our results indicate that CLL cell doublets were in the cytokinesis stage of the cell cycle, specifically, after reformation of the nucleus, but before abscission and physical separation of the cytoplasm 11, 13, 14, 15, 16…”

“…The described Actin, Tubulin and Plk1 localization corresponds to late steps of cytokinesis, more precisely, to the step after nuclear envelope reformation and chromosome decondensation, but before cytoplasmic abscission by the contractile ring between the 2 daughter cells 11, 13, 14, 15, 16. Previous studies have linked cytokinesis defects, multiple centrosomes and accumulation of cells in G0/1 to be a consequence of dysregulation of important players in cell cycle regulation 34.…”

Mitotic crisis: The unmasking of a novel role for RPA

“…Plk1 (and its ortholog Cdc5 in budding yeast) is an essential serine/threonine kinase that regulates both mitotic entry and cytokinesis in eukaryotes (reviewed in Petronczki et al 13 ). Among its key substrates are the Cdc25C phosphatase, with phosphorylation stimulating Ccd25C action towards cyclin B1-Cdk1 and activating the kinase complex for mitotic entry; and the anaphase-promoting complex (APC), the latter event leading to APC activation and anaphase onset.…”

Quantitative Phospho-proteomics to Investigate the Polo-like Kinase 1-Dependent Phospho-proteome

“…In mitosis, several other kinases, including Aurora A and B (AURKA/B) and PLK1, are activated to orchestrate the different events that are required for chromosome segregation and subsequent cell division. PLK1 has several essential roles during mitotic entry, early mitosis, and late mitosis (1,2). Before mitotic entry, PLK1 is required for the release from a DNA-damage-induced G2-phase arrest (3).…”

“…Progression through the cell cycle is controlled by cyclindependent kinases (CDKs) 1 . In mitosis, several other kinases, including Aurora A and B (AURKA/B) and PLK1, are activated to orchestrate the different events that are required for chromosome segregation and subsequent cell division.…”