Serine/threonine-protein kinase PLK4 (PLK4)

Serine/threonine-protein kinase PLK4, also known as Polo-like kinase 4, is a master regulator of centriole duplication and centrosome biogenesis (UniProt, 2024). It localizes to the centrioles and ensures they are replicated exactly once per cell cycle, maintaining genomic stability (PubMed, 2019). Dysregulation or overexpression of PLK4 is frequently observed in various malignancies, including breast, lung, and gastric cancers, where it drives centrosome amplification and chromosomal instability (PMC, 2021). This makes PLK4 a compelling therapeutic target, as its inhibition can selectively induce mitotic catastrophe and apoptosis in cancer cells (Patsnap Synapse, 2024). Small molecule inhibitors like CFI-400945 and RP-1664 are currently being evaluated in clinical trials for their ability to disrupt the cell cycle in tumor cells (Repare Therapeutics, 2023). These drugs typically act as ATP-competitive inhibitors that block the kinase activity of PLK4 (PMC, 2020). Additionally, PLK4 inhibition has shown synthetic lethality in tumors with TRIM37 amplification, providing a potential biomarker for patient selection (OIST, 2023).

Other names

Polo-like kinase 4Serine/threonine-protein kinase 18Serine/threonine-protein kinase SAKSTK18

ATP-competitive inhibition of the PLK4 kinase domain, which prevents the phosphorylation of substrates necessary for centriole duplication, thereby inducing mitotic arrest and apoptosis.