(Plks) are important regulators of the cell cycle
. Plks are involved in the formation of and the changes in the mitotic spindle and in the activation of CDK/cyclin
complexes during the M-phase of mitosis
.Polo-like kinases (Plks) are a family of conserved serine/threonine kinases involved in the regulation of cell cycle progression through G2 and M mitosis
. Mammalian polo-like kinases include Plk1 (Xenopus Plx1), Plk2/Snk (Xenopus Plx2), Plk3/Prk/FnK (Xenopus Plx3) and Plk4/Sak. Most species have only one form of Plk; Drosophila (Polo), Schizosaccharomyces pombe (Plo1) and Saccharomyces cerevisiae (Cdc5). Polo-like kinases are involved in aspects of mitosis that include mitotic entry and exit and cytokinesis
[http://genesdev.cshlp.org/content/12/24/3777.full "IPolo-like kinases: a team that plays throughout mitosis"]
The catalytic domain of polo-like kinases is located in the N-terminus. The C-terminus of Plks contains one or two motifs known as polo boxes that help localize the kinase to specific mitotic structures during mitosis. These include the centrosomes in early M phase, the spindle midzone in early and late anaphase and the midbody during cytokinesis.
[http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&cmd=prlinks&retmode=ref&id=8510757"A conserved mitotic kinase active at late anaphase—telophase in syncytial Drosophila embryos"]
Cell Cycle Regulation
Plks mediate G2/M transitions, activation of cdc25
and mitotic processes including centrosome maturation, bipolar spindle formation, activation of the anaphase-promoting complex (APC), chromosome segregation, and actin ring formation (cytokinesis).
Plk1 is an early trigger for G2/M transition. Plk1 supports the functional maturation of the centrosome in late G2/early prophase and establishment of the bipolar spindle. Plk1 phosphorylates and activates cdc25C, a phosphatase that dephosphorylates and activates the cyclinB/cdc2 complex. Plk phosphorylates and activates components of the APC. The APC, which is activated by Fizzy-Cdc20 family proteins, is a cell cycle ubiquitin-protein ligase (E3) that degrades mitotic cyclins, chromosomal proteins that maintain cohesion of sister chromatids, and anaphase inhibitors. Abnormal spindle (Asp), a Polo kinase substrate, is a microtubule-associated protein essential for correct behavior of spindle poles and M-phase microtubules. Plk1 localizes to the central region of the spindle in late mitosis and associates with kinesin-like protein CHO1/MKLP1. The homologous motor protein in Drosophila is the pavarotti gene product (PAR).
Plk3 is a multifunctional stress response protein that responses to signals induced by DNA damage and/or mitotic spindle disruption.
[http://www.ncbi.nlm.nih.gov/pubmed/16627997?dopt=Abstract&holding=f1000,f1000m,isrctn"Polo-like kinases: a team in control of the division."]
Role in Tumorigenesis
Plk1 is considered a proto-oncogene, whose overexpression is often observed in tumor cells. Aneuploidy and tumorigenesis can also result from centrosome abnormality, particularly centrosome amplification defects. Centrosome duplication and maturation regulated by Plk1 occurs from late S phase to prophase. Abnormal centrosome amplification may lead to multipolar spindles and results in unequal segregation of chromosomes.Plk1 overexpression also increases the centrosome size and/or centrosome number, which will also lead to improper segregation of chromosomes, aneuploidy, and tumorigenesis.
[http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6VS0-4MRNCM9-1&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=677ef7303e5efeb73f48f8d77440556f"Cell cycle kinases in cancer"]
Plk3 substrates include Chk2 and p53.
Described and named in 1993.
[http://www.pnas.org/content/90/11/4882.abstract "Identification and cloning of a protein kinase-encoding mouse gene, Plk, related to the polo gene of Drosophila"]