Cyclin-dependent kinase 9

Cyclin-dependent kinase 9

Crystal structure of Cyclin-dependent kinase 9 (CDK9)

Cyclin-dependent kinase 9 (CDK9) is a protein kinase that plays a crucial role in regulating the cell cycle and transcriptional elongation. It is a member of the cyclin-dependent kinase (CDK) family and is involved in various cellular processes, including cell growth, differentiation, and apoptosis.

Structure

CDK9 is composed of 372 amino acids and has a molecular weight of approximately 42 kDa. It consists of three main domains: the N-terminal domain, the kinase domain, and the C-terminal domain. The N-terminal domain is responsible for protein-protein interactions, while the kinase domain catalyzes the transfer of phosphate groups to target proteins. The C-terminal domain is involved in the regulation of CDK9 activity.

Function

CDK9 forms a complex with its regulatory partner, cyclin T, to form the positive transcription elongation factor b (P-TEFb) complex. This complex phosphorylates the C-terminal domain of RNA polymerase II, allowing for the efficient transcriptional elongation of genes. CDK9 also phosphorylates other transcription factors and chromatin-associated proteins, thereby regulating gene expression.

Furthermore, CDK9 is involved in the regulation of the cell cycle. It phosphorylates the retinoblastoma protein (Rb), leading to the release of E2F transcription factors and the progression of the cell cycle from G1 to S phase. CDK9 also regulates the expression of cyclins and cyclin-dependent kinase inhibitors, which are essential for cell cycle progression.

Role in Disease

CDK9 has been implicated in various diseases, including cancer and viral infections. In cancer, CDK9 is often overexpressed or hyperactivated, leading to uncontrolled cell proliferation and tumor growth. Targeting CDK9 has emerged as a potential therapeutic strategy for cancer treatment.

In viral infections, CDK9 plays a critical role in the replication of certain viruses, such as human immunodeficiency virus (HIV). CDK9 inhibitors have shown promise in inhibiting viral replication and may have therapeutic potential in the treatment of viral infections.

See Also

• Cyclin-dependent kinase
• Cell cycle
• Transcription
• RNA polymerase II
• Positive transcription elongation factor b