positive regulation of cyclin-dependent protein kinase activity

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of cyclin-dependent protein kinase activity. [GO_REF:0000059, GOC:als, GOC:TermGenie, PMID:22995177]

Positive regulation of cyclin-dependent protein kinase (CDK) activity is a crucial cellular process that governs cell cycle progression, DNA replication, and other essential cellular functions. CDKs are a family of serine/threonine protein kinases that regulate the transition between different phases of the cell cycle. Their activity is tightly controlled by the binding of regulatory subunits known as cyclins.

The activation of CDKs involves a multi-step process:

1. **Cyclin Binding:** CDKs are inactive in their monomeric form. Binding of a specific cyclin to the CDK subunit is the first step towards activation. Cyclins are regulatory proteins that exhibit cyclical expression patterns during the cell cycle. Different cyclins associate with specific CDKs to form complexes that regulate distinct phases of the cell cycle.

2. **Phosphorylation by Activating Kinases:** Once the cyclin-CDK complex is formed, it undergoes further activation through phosphorylation. Cyclin-dependent kinase-activating kinase (CAK) phosphorylates a specific threonine residue on the CDK subunit, which is essential for full enzymatic activity.

3. **Dephosphorylation of Inhibitory Sites:** In some cases, CDKs are further regulated by the phosphorylation of inhibitory sites on the CDK subunit. These inhibitory phosphorylations are reversed by phosphatases, leading to full activation of the complex.

4. **CDK Inhibitors:** The activity of CDKs can also be regulated by the binding of specific inhibitory proteins known as CDK inhibitors (CKIs). These proteins bind to and inactivate CDK-cyclin complexes, preventing their activity.

**Mechanism of Action:**

Activated CDKs phosphorylate a variety of downstream target proteins, including transcription factors, DNA replication machinery, and other regulatory proteins. These phosphorylation events trigger a cascade of events that promote cell cycle progression. For example, phosphorylation of the retinoblastoma protein (Rb) by CDK4/6-cyclin D complexes releases the E2F transcription factor, which in turn activates the expression of genes required for DNA replication.

**Dysregulation in Disease:**

Dysregulation of positive regulation of CDK activity is implicated in various diseases, including cancer. Overexpression or mutations in CDK genes or their regulators can lead to uncontrolled cell proliferation and tumor growth. Conversely, inactivation of CDKs or their activating factors can cause developmental defects and cell cycle arrest.

**In Summary:** Positive regulation of CDK activity is a highly regulated process that ensures proper timing and coordination of cell cycle events. Disruption of this regulation can lead to serious consequences for cell growth and development.'
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Proteins (1)

Compounds (2)