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Cyclin-dependent kinase 16 (CDK16), also called PCTAIRE1 or PCTK1, is an atypical member of the cyclin-dependent kinase family that functions as a serine/threonine-protein kinase. It is activated via interaction with cyclin Y and 14-3-3 proteins in a phosphorylation-dependent manner. CDK16 is highly expressed in the testis and brain, where it regulates key processes such as spermatogenesis and neurite outgrowth; it also influences vesicle trafficking, exocytosis, muscle differentiation, and glucose homeostasis. Genetic knockout studies demonstrate its essential role in male fertility: CDK16 deficiency leads to impaired sperm motility and morphology. CDK16 is implicated in cancer cell proliferation and migration, and targeting its ATP-binding site with kinase inhibitors such as dabrafenib, rebastinib, and indirubin E804 offers pharmacological intervention potential. Its structural and mechanistic properties distinguish it from classical CDKs, notably its unique PCTAIRE cyclin-binding motif and requirement for cyclin partners for full activity. In clinical and laboratory settings, CDK16 is under exploration as both a therapeutic target in cancer and a biomarker in reproductive health.
Kinase inhibition (by drugs targeting the ATP-binding pocket, e.g. both type I and II kinase inhibitors; dabrafenib and rebastinib specifically stabilize inactive conformations of CDK16)
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