The mammalian polo-like kinase-3 (Plk3): A role in cell cycle regulation and apoptosis

The polo-like kinases (PLK's) comprise a family of conserved serine/threonine protein kinases that play a critical role in the normal progression of cells through mitosis. The Plk3 serine/threonine kinase is a mammalian member of this family. Analysis of Plk3 expression revealed that Plk3 protein levels do not fluctuate as a function of cell cycle progression. Overexpression of Plk3 in mammalian cells suppresses proliferation and inhibits colony formation. Subsequent analysis demonstrated that overexpression of Plk3 induces chromatin condensation and apoptosis. This phenotype could not be inhibited by co-expression of Bcl-2 and was partially dependent on the COOH-terminal domain of Plk3 but not on the catalytic activity of Plk3. Furthermore, the ability of Plk3 to induce apoptosis is independent of proliferation. Analysis of EGFP-Plk3 subcellular localization revealed that Plk3 localizes to the cellular cortex and to the cell midbody during exit from mitosis and is consistent with a role in cytokinesis. Additionally, overexpression of Plk3 results in incomplete cytokinesis and cell cycle arrest. Biochemical analysis of Plk3 revealed that Plk3 co-immunoprecipitates with components of the anaphase-promoting complex. These data suggest that overexpression or ectopic suppression of Plk3 interferes with cellular proliferation by impeding cytokinesis and that like other Plks, Plk3 is likely to play a role in regulation of the cell cycle by ubiquitin mediated proteolysis.