Abstract
The Polo kinase is an essential regulator of cell division. Its ability to regulate multiple events at distinct subcellular locations and times during mitosis is remarkable. In the last few years, a much clearer mechanistic understanding of the functions and regulation of Polo in cell division has emerged. In this regard, the importance of coupling changes in activity with changes in localization is striking, both for Polo itself and for its upstream regulators. This review brings together several new pieces of the puzzle that are gradually revealing how Polo is regulated, in space and time, to enable its functions in the early stages of mitosis in animal cells. As a result, a unified view of how mitotic entry is spatio-temporally regulated is emerging.
Highlights
To regulate these different functions, Polo must be activated and dynamically recruited to distinct subcellular structures, in space and time [10]
As Cyclin B –Cdk1 is the central trigger of mitotic entry, defined by nuclear envelope breakdown (NEB) and chromosome condensation, these results implied that Polo should be required for mitotic entry, acting upstream of Cyclin B –Cdk1 [17]
The phenotypes of the polo mutants isolated in Drosophila suggested that Polo was needed for cells to assemble functional mitotic centrosomes and a bipolar spindle, but mutant neuroblasts did enter mitosis [1]
Summary
Discovered in Drosophila, Polo gave its name to the Polo-like kinase (PLK) family, five of which exist in humans ( Plk is kinase-inactive) [1,2]. Drosophila Polo, mammalian Plk, Xenopus Plx and Caenorhabditis elegans PLK-1 are clear orthologues at the sequence and functional levels (here, we refer to them collectively as Polo) These Ser/Thr kinases are defined by the presence of an N-terminal kinase domain (KD) and an additional C-terminal domain, termed the Polo-box domain (PBD), which engages in protein interactions [3,4]. The kinase activity, PBD interactions, interdomain inhibition and localization of Polo are all subjected to regulation by posttranslational modifications and structural changes [3]. Because these mechanisms work together to control Polo, they need to be understood at the molecular level to fully appreciate the place Polo occupies on the central stage of cell division. License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited
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