positive regulation of cyclin-dependent protein serine/threonine kinase activity

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of CDK activity. [GOC:go_curators, GOC:pr]

Positive regulation of cyclin-dependent protein serine/threonine kinase activity is a crucial process in the cell cycle, ensuring proper timing and execution of crucial events like DNA replication and cell division. It involves a complex interplay of regulatory proteins that activate cyclin-dependent kinases (CDKs), key enzymes responsible for phosphorylating target proteins and driving cell cycle progression.

The process begins with the synthesis of CDK proteins, which remain inactive in their monomeric state. To become functional, CDKs must associate with regulatory subunits called cyclins. Cyclins are proteins whose levels fluctuate throughout the cell cycle, providing temporal control over CDK activity. The binding of a cyclin to a CDK forms a heterodimer, the active form of the enzyme.

However, even cyclin-bound CDKs are not fully active. Further regulation is provided by activating and inhibitory phosphorylation events. Activating phosphorylation occurs on specific residues within the CDK, usually by another kinase, leading to conformational changes that enhance the CDK's catalytic activity. In contrast, inhibitory phosphorylation at different sites can block CDK activity, preventing premature cell cycle progression.

The activation state of CDKs is also influenced by the presence of CDK inhibitors (CKIs). CKIs are small proteins that bind to CDK-cyclin complexes and directly block their activity. The interplay between activating and inhibitory phosphorylations, along with the binding of CKIs, precisely regulates CDK activity throughout the cell cycle.

Once activated, CDK-cyclin complexes phosphorylate a wide array of target proteins involved in various cell cycle processes. For example, CDK1-cyclin B complexes trigger entry into mitosis, while CDK2-cyclin E complexes promote DNA replication. This phosphorylation cascade ensures that events occur in the correct sequence and at the right time, preventing uncontrolled cell growth and maintaining genomic integrity.

Positive regulation of CDK activity is tightly controlled by a multitude of factors, including cell signaling pathways, DNA damage response, and external cues. Dysregulation of this process can lead to uncontrolled cell proliferation, a hallmark of cancer. Therefore, understanding the intricate mechanisms of CDK regulation is essential for developing targeted therapies against cancer and other diseases.
'"

Proteins (7)

Compounds (1,038)