Function
Cyclin-dependent kinase 6 (CDK6) is a serine/threonine-protein kinase that plays a pivotal role in regulating cell cycle progression and differentiation. Notably, CDK6 promotes the transition from the G1 to S phase of the cell cycle. This function is mediated by its phosphorylation of key proteins like pRB/RB1 and NPM1. During interphase, CDK6 interacts with D-type G1 cyclins, forming a complex that acts as a pRB/RB1 kinase. This complex controls entry into the cell cycle. CDK6 also contributes to cell cycle exit during differentiation, preventing uncontrolled proliferation and negatively regulating differentiation. However, CDK6 is essential for the proliferation of specific cell types, such as erythroid and hematopoietic cells. Furthermore, CDK6 is crucial for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles, indicating its role in neurogenesis. CDK6 is also required during thymocyte development. In addition to its role in cell cycle regulation, CDK6 contributes to the production of newborn neurons, likely by modulating G1 length. Interestingly, in astrocytes, CDK6 promotes changes in gene expression patterns, alterations in the actin cytoskeleton (including the loss of stress fibers), and enhanced motility during differentiation. CDK6 also exhibits an inhibitory effect on myeloid differentiation by interfering with RUNX1 and reducing its transcriptional transactivation activity. Conversely, it promotes the proliferation of normal myeloid progenitors. Moreover, CDK6 delays senescence and promotes the proliferation of beta-cells in pancreatic islets of Langerhans. Lastly, CDK6 may play a role in centrosome organization during the cell cycle phases.