Polo-like kinase 3 is required for entry into S phase

The polo-like kinase, Plk1, which is expressed and active in mitosis, is involved in regulation of mitotic entry, spindle pole assembly, mitotic exit, and cytokinesis [Donaldson MM, Tavares AA, Hagan IM, Nigg EA, Glover DM (2001) J Cell Sci 114:2357-2358]. In mammals, there are two other members of the polo-like kinase family that are less well understood, Plk2 and Plk3. Plk3 first was identif ied and cloned as an immediate early gene. Here, we report Plk3 localizes to the nucleolus and is involved in regulation of the G(1)/S phase transition. We demonstrate that the level of Plk3 protein is cell cycle regulated, peaking in G(1). We have delivered Plk3interfering RNA with lentivirus to serum-starved cells and found that, upon serum stimulation, Plk3 is required for cyclin E expression and entry into S phase. Plk3-interfering RNA-induced Plk3 depletion resulted in a large fraction of asynchronously proliferating cells to become quiescent. We propose the Plk3 requirement in the cell cycle is fulfilled in G1, and that once cells pass this point, they are able to complete cell division, whereas in the absence of Plk3, they fail to reenter the cell cycle. Additional data suggest that Plk3 may regulate entry into S phase in part through interaction with the phosphatase Cdc25A, because its depletion also resulted in attenuation of cyclin E expression.