CDK-activating kinase

CDK-activating kinase (CAK) is a crucial enzyme involved in the regulation of the cell cycle. It plays a vital role in the activation of cyclin-dependent kinases (CDKs), which are key regulators of cell division and proliferation. In this article, we will explore the structure, function, and significance of CDK-activating kinase.

Structure

CDK-activating kinase is a heterotrimeric protein complex composed of three subunits: cyclin-dependent kinase 7 (CDK7), cyclin H, and Mat1. CDK7 serves as the catalytic subunit, while cyclin H and Mat1 act as regulatory subunits. The complex is highly conserved across eukaryotes, indicating its fundamental role in cell cycle control.

Function

The primary function of CDK-activating kinase is to phosphorylate and activate CDKs. CDKs are inactive in their unphosphorylated state and require phosphorylation at a specific site, known as the T-loop, for activation. CDK7, as part of the CAK complex, phosphorylates this T-loop, leading to the activation of CDKs.

CDKs, once activated, regulate various cellular processes, including DNA replication, transcription, and cell division. By activating CDKs, CDK-activating kinase plays a crucial role in coordinating these processes and ensuring proper cell cycle progression.

Significance

The activity of CDK-activating kinase is tightly regulated to maintain the balance between cell proliferation and cell cycle arrest. Dysregulation of CAK activity has been implicated in various diseases, including cancer. Abnormal activation of CDKs due to CAK dysregulation can lead to uncontrolled cell division and tumor formation.

Furthermore, CDK-activating kinase has been identified as a potential therapeutic target for cancer treatment. Inhibitors of CDK7, such as THZ1, have shown promising results in preclinical studies and are currently being evaluated in clinical trials. Targeting CDK-activating kinase provides a strategy to selectively inhibit cell proliferation in cancer cells while sparing normal cells.

See Also

• Cyclin-dependent kinases
• Cell cycle regulation
• Cancer biology