PLK

PLK, short for Polo-like kinase, refers to a family of conserved serine/threonine kinases that coordinate various aspects of cell division. In humans, the best-studied member is PLK1, which is essential for progression through mitosis, including centrosome maturation, spindle formation, chromosome segregation, and cytokinesis. Other family members include PLK2, PLK3, PLK4, and PLK5, the latter of which is largely described as brain-expressed and lacks robust catalytic activity in many contexts.

PLKs share a common two-domain structure: an N-terminal kinase domain responsible for catalytic activity and a C-terminal polo-box domain (PBD) that mediates substrate binding and subcellular localization. The PBD targets PLKs to specific mitotic structures by recognizing phosphorylated docking motifs, enabling precise phosphorylation of substrates. Activation and localization are tightly regulated by phosphorylation and interactions with partners, with PLK1 activation frequently involving upstream kinases such as Aurora A in mitosis.

Functions across the cell cycle vary by member. PLK1 governs entry into and progression through mitosis, including centrosome maturation, spindle assembly, chromosome alignment, and cytokinesis. PLK2 and PLK3 participate in stress responses and differentiation signals. PLK4 is critical for centriole duplication, and PLK5 has a more limited, but not fully understood, role in humans.

Clinical relevance: PLK1 is often overexpressed in cancers and associated with poor prognosis. Because of its central role in cell division, PLK inhibitors have been developed and tested in clinical trials, with agents like volasertib and onvansertib explored as anticancer therapies. Development has faced challenges related to toxicity and resistance, but PLK remains a target of interest in oncology research.