At least 4 distinct polo-like kinases exist in mammalian cells: PLK1, PLK2, PLK3 and PLK4/SAK. Like the other PLK family members, PLK3 contains an amino-terminal catalytic domain and a conserved carboxy-terminal domain termed the Polo box. PLK3, also called proliferation-related kinase (Prk), was originally described as a fibroblast growth factor (FGF)-inducible kinase (Fnk) and identified as an immediate-early response gene responsive to FGF-1 and other mitogens. PLK3 is a cytokine-inducible serine/threonine kinase whose protein expression is cell cycle regulated. Though its expression is found primarily in G1 phase of the cell cycle, PLK3 is detected in G0 and in late telophase prior to cytokinesis. Like the other PLK family members, PLK3 functions mainly as a regulator of the cell cycle. Specifically, PLK3 is required for entry into S phase and is a critical regulator of G1 events, as indicated by RNAi-induced PLK3-depleted cells. PLK3 is also involved in the regulation of DNA damage response via phosphorylation of p53 on Ser20. PLK3 may act as a tumor suppressor as Plk3-deficient mice develop spontaneous tumors in various organs. Unlike PLK1, PLK3 expression is down regulated in cancers including lung, head and neck, and colon.
