Cyclin-dependent kinase 6

Cyclin-dependent kinase 6 (CDK6)

Cyclin-dependent kinase 6 (CDK6) is a protein that in humans is encoded by the CDK6 gene. CDK6 is a member of the cyclin-dependent kinase family, which is a group of serine/threonine protein kinases involved in regulating the cell cycle.

Structure

CDK6 is a protein kinase that is activated by binding to a regulatory subunit known as a cyclin. The structure of CDK6 includes a catalytic domain that is typical of protein kinases, with an ATP-binding site and a substrate-binding site. The activation of CDK6 requires phosphorylation at specific residues and binding to D-type cyclins, such as Cyclin D1, Cyclin D2, and Cyclin D3.

Function

CDK6 plays a crucial role in the regulation of the cell cycle, particularly during the transition from the G1 phase to the S phase. It forms a complex with D-type cyclins, which leads to the phosphorylation of the retinoblastoma protein (Rb). Phosphorylation of Rb results in the release of E2F transcription factors, which then activate the transcription of genes required for DNA synthesis and cell cycle progression.

Clinical Significance

CDK6 is implicated in various types of cancer. Overexpression or amplification of the CDK6 gene can lead to uncontrolled cell proliferation, a hallmark of cancer. CDK6 inhibitors, such as Palbociclib, Ribociclib, and Abemaciclib, have been developed as targeted therapies for cancers that exhibit dysregulation of the CDK4/6 pathway.

Research and Development

Research on CDK6 continues to explore its role in cancer and other diseases. Studies are investigating the potential of CDK6 inhibitors in combination with other therapies to enhance their efficacy and overcome resistance mechanisms.

See Also

• Cyclin-dependent kinase
• Cell cycle
• Cancer

External Links

• CDK6 Gene - NCBI
• CDK6 Protein - UniProt