Polo-like kinases and the orchestration of cell division

The genomic stability of all eukaryotic organisms depends on the error-free segregation of chromosomes during mitotic and meiotic cell divisions.Polo-like kinases (Plks) are conserved regulators of several stages of mitosis and meiosis, and transiently associate with many mitotic structures such as centrosomes and spindle poles, kinetochores and the central spindle.Plks have a similar architecture, with a canonical serine/threonine kinase domain at the amino terminus and a carboxy-terminal regulatory domain that contains two signature motifs, known as polo boxes. The polo-box domain (PBD) binds to phosphopeptides and is required for Plk localization and activation.Plks are activated by direct phosphorylation within the kinase domain by upstream kinases and via the binding of the PBD to phosphorylated docking proteins. Plk1 has maximal activity in mitosis and is then rapidly targeted by the APC/C–Cdh1 pathway for degradation by the proteasome as cells exit mitosis.Plk1 contributes to the entry into mitosis through the regulation of kinases (Wee1/Myt1) and phosphatases (Cdc25 family members) that function in an important regulatory loop that controls the activation of the Cdk1–cyclin-B mitotic kinase. Plk1 is also important for the maturation of the centrosomes at the G2/M transition, which leads to increased microtubule nucleation and bipolar spindle formation.Plks have been localized to kinetochores and shown to phosphorylate the APC/C ubiquitin ligase, which suggests that they have a role in chromosome segregation.Plks are implicated in signalling pathways that control mitotic exit and cytokinesis, although the precise details of this regulation differ depending on the organism.