Cyclin-dependent kinase inhibitor

Cyclin-dependent kinase inhibitors (CDK inhibitors) are a class of proteins that regulate the cell cycle by inhibiting the activity of cyclin-dependent kinases (CDKs). These inhibitors play a crucial role in controlling cell division and ensuring that cells do not proliferate uncontrollably, which is a hallmark of cancer.

Structure and Function

CDK inhibitors are divided into two main families: the INK4 family and the Cip/Kip family.

INK4 Family

The INK4 family includes proteins such as p16^INK4a, p15^INK4b, p18^INK4c, and p19^INK4d. These proteins specifically inhibit CDK4 and CDK6, preventing them from associating with D-type cyclins. This inhibition blocks the progression from the G1 phase to the S phase of the cell cycle.

Cip/Kip Family

The Cip/Kip family includes p21^Cip1, p27^Kip1, and p57^Kip2. These inhibitors have a broader range of targets and can inhibit multiple CDKs, including CDK2, CDK4, and CDK6. They function by binding to cyclin-CDK complexes and inhibiting their kinase activity.

Role in Cancer

CDK inhibitors are critical in preventing uncontrolled cell proliferation. Mutations or deletions in genes encoding these inhibitors can lead to the loss of cell cycle control, contributing to the development of cancer. For example, the loss of p16^INK4a is commonly observed in melanoma and other cancers.

Therapeutic Applications

CDK inhibitors have been developed as therapeutic agents in cancer treatment. These drugs aim to restore cell cycle control in cancer cells. Examples of CDK inhibitors used in therapy include palbociclib, ribociclib, and abemaciclib, which are primarily used in the treatment of breast cancer.

Research and Development

Ongoing research is focused on developing more selective CDK inhibitors with fewer side effects. Understanding the specific roles of different CDK inhibitors in various types of cancer is crucial for developing targeted therapies.

Also see

• Cell cycle
• Cyclin-dependent kinase
• Cancer therapy
• Tumor suppressor gene