Cyclin-dependent kinase

Function

Cyclin-dependent kinase (CDK) or Cell division protein kinase are serine/threonine kinases which are important to the regulation of the cell cycle. CDKs are small proteins which contain just a kinase domain. In order to function, CDK binds the regulatory protein cyclin. CDKs phosphorylate their substrates at a consensus tetrapeptide. The CDK classes differ by the binding cyclin and their function in human.^[1]

• CDK1 binds cyclin and forms a complex which phosphorylates a variety of substrates which are involved in cell cycle progression.

• CDK2 is involved in the control of the cell cycle. It interacts with the regulatory protein cyclin A2. Phosphorylation at Thr14 or Tyr15 inactivates it; phosphorylation at Thr160 (T160P) – activates it. See also Intrinsically Disordered Protein.
• CDK3 binds cyclin C and functions during the G1 phase.
• For details on CDK4 see Cyclin Dependent Kinase-4.

• CDK5 binds p53 and functions during transcription.
  

• CDK6 binds cyclin D and functions during the G1 phase.
• CDK7 may serve as a direct link between transcription regulation and the cell cycle.
• CDK8 binds cyclin C and functions during transcription.
• CDK12 phosphorylates the C-terminal domain of the large subunit of RNA polymerase II. Acts as a regulator of transcription elongation.
• CDK16 plays a role in vesicle-mediated transport processes and exocytosis.

Relevance

CDK is a potential target for anti-cancer therapy.

Structural highlights

The kinase ATP-binding active site is located in a cleft between the small N-lobe and the large C-lobe. Phosphorylated Thr near the binding site is required for kinase activity.^[2]