Regulation of cell cycle checkpoints by polo-like kinases.

Protein kinases play a pivotal role in execution of cell division. Polo and Polo-like kinases have emerged as major regulators for various cell cycle checkpoints. Early genetic studies have demonstrated that CDC5, a budding yeast counterpart of vertebrate Plks, is essential for successful mitotic progression. Mammalian Plks localize primarily to the centrosome during interphase and the mitotic apparatus during mitosis. Many key cell cycle regulators such as p53, Cdc25C, cyclin B, components of the anaphase-promoting complex, and mitotic motor proteins are directly targeted by Plks. Although the exact mechanism of action of these protein kinases in vivo remains to be elucidated, Plks are important mediators for various cell cycle checkpoints that monitor centrosome duplication, DNA replication, formation of bipolar mitotic spindle, segregation of chromosomes, and mitotic exit, thus protecting cells against genetic instability during cell division.