Cyclin-dependent kinase 16 (CDK16), also known as PCTAIRE1, is a member of the cyclin-dependent kinase (CDK) family, which plays a crucial role in regulating various cellular processes. Unlike typical CDKs that are primarily involved in cell cycle regulation, CDK16 is classified as an atypical CDK due to its unique structure and functions. CDK16 is predominantly expressed in terminally differentiated cells, such as neurons and testis, and is involved in processes like exocytosis, vesicle-mediated transport, and signal transduction .
CDK16 belongs to the PCTAIRE family, which includes CDK16, CDK17, and CDK18. These kinases are characterized by a highly conserved kinase domain that is closely related to those of cell cycle-regulating CDKs . CDK16’s activity is dependent on its interaction with Cyclin Y (CCNY), which regulates its kinase activity. This interaction is essential for CDK16’s role in various cellular processes, including the regulation of insulin secretion, spermatogenesis, and neuron differentiation .
CDK16 has been implicated in several critical biological processes. It plays a role in the regulation of insulin secretion in response to changes in blood glucose levels, which is vital for maintaining glucose homeostasis . Additionally, CDK16 is required for normal spermatogenesis, highlighting its importance in reproductive biology . In neurons, CDK16 regulates differentiation and dendrite development, contributing to proper neuronal function .
Recent studies have shown that CDK16 is highly expressed in certain types of cancer, particularly triple-negative breast cancer (TNBC). Elevated CDK16 expression is correlated with poor outcomes in breast cancer patients, making it a potential therapeutic target . CDK16 promotes the proliferation and migration of TNBC cells by phosphorylating protein regulator of cytokinesis 1 (PRC1), which is involved in spindle formation during mitosis . Both genetic knockdown and pharmacological inhibition of CDK16 have been shown to significantly suppress tumor progression in TNBC .