Cyclin-dependent kinases

Cyclin-dependent kinases

Cyclin-dependent kinases (CDKs) are a family of protein kinases first discovered for their role in regulating the cell cycle. They are also involved in regulating transcription, mRNA processing, and the differentiation of nerve cells. CDKs are present in all known eukaryotes and their regulatory function is highly conserved.

Structure and Function

CDKs are serine/threonine kinases that require a separate subunit, a cyclin, for their activity. The binding of a cyclin to a CDK activates the kinase, allowing it to phosphorylate target proteins. This phosphorylation results in the progression of the cell cycle through its various phases.

Cyclin Binding

Cyclins are proteins that vary in concentration throughout the cell cycle. The binding of a cyclin to a CDK is necessary for the activation of the kinase. Different cyclins are expressed at different stages of the cell cycle, ensuring that CDKs are activated only at the appropriate times.

Regulation

CDK activity is regulated by several mechanisms:

• Cyclin availability: The presence of specific cyclins is required for CDK activation.
• Phosphorylation: CDKs can be activated or inactivated by phosphorylation at specific sites.
• CDK inhibitors (CKIs): Proteins such as p21, p27, and p16 can bind to CDKs and inhibit their activity.

Role in the Cell Cycle

CDKs are crucial for the control of the cell cycle. They ensure that the cell cycle progresses in an orderly manner, preventing errors such as DNA damage or incomplete replication.

G1 Phase

In the G1 phase, CDK4 and CDK6, in association with cyclin D, are responsible for the progression through the G1 phase and the initiation of the S phase.

S Phase

During the S phase, CDK2, in complex with cyclin E, is responsible for the initiation of DNA replication.

G2 Phase

In the G2 phase, CDK1, in association with cyclin A, prepares the cell for mitosis.

Mitosis

CDK1, in complex with cyclin B, is essential for the initiation of mitosis. This complex is often referred to as the maturation-promoting factor (MPF).

Clinical Significance

Dysregulation of CDK activity is a hallmark of cancer. Overexpression of cyclins or mutations in CDKs can lead to uncontrolled cell proliferation. As a result, CDKs are targets for cancer therapy. CDK inhibitors, such as palbociclib, are used in the treatment of certain types of cancer.

Research and Development

Ongoing research is focused on understanding the precise mechanisms of CDK regulation and their role in various cellular processes. This research is crucial for the development of new therapeutic strategies for diseases such as cancer.

See Also

• Cell cycle
• Protein kinase
• Cyclin

References

• Morgan, D. O. (2007). "The Cell Cycle: Principles of Control." Oxford University Press.
• Sherr, C. J., & Roberts, J. M. (1999). "CDK inhibitors: positive and negative regulators of G1-phase progression." Genes & Development, 13(12), 1501-1512.