Cyclin-Dependent Protein Kinases

Cdks (cyclin-dependent kinases) are heteromeric serine/threonine kinases that control progression through the cell cycle in concert with their regulatory subunits, the cyclins. Although there are 12 different cdk genes, only 5 have been shown to directly drive the cell cycle (Cdk1, -2, -3, -4, and -6).

Following extracellular mitogenic stimuli, cyclin D gene expression is upregulated. Cdk4 forms a complex with cyclin D and phosphorylates Rb protein, leading to liberation of the transcription factor E2F. E2F induces transcription of genes including cyclins A and E, DNA polymerase and thymidine kinase. Cdk4-cyclin E complexes form and initiate G₁/S transition. Subsequently, Cdk1-cyclin B complexes form and induce G₂/M phase transition. Cdk1-cyclin B activation induces the breakdown of the nuclear envelope and the initiation of mitosis.

Cdks are constitutively expressed and are regulated by several kinases and phosphastases, including Wee1, CDK-activating kinase and Cdc25 phosphatase. In addition, cyclin expression is induced by molecular signals at specific points of the cell cycle, leading to activation of Cdks. Tight control of Cdks is essential as misregulation can induce unscheduled proliferation, and genomic and chromosomal instability. Cdk4 has been shown to be mutated in some types of cancer, whilst a chromosomal rearrangement can lead to Cdk6 overexpression in lymphoma, leukemia and melanoma. Cdks are currently under investigation as potential targets for antineoplastic therapy, but as Cdks are essential for driving each cell cycle phase, therapeutic strategies that block Cdk activity are unlikely to selectively target tumor cells.

External sources of pharmacological information for Cyclin-Dependent Protein Kinases :

• BJP Guide

Literature for Cyclin-Dependent Protein Kinases

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Cancer Research Product Guide

A collection of over 750 products for cancer research, the guide includes research tools for the study of:

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Kinases Product Listing

A collection of over 400 products for kinase research, the listing includes inhibitors of:

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• MAPK Signaling
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Neurodegeneration Product Guide

A collection of over 275 products for neurodegeneration research, the guide includes research tools for the study of:

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Cell Cycle & DNA Damage Repair Poster

In normal cells, each stage of the cell cycle is tightly regulated, however in cancer cells many genes and proteins that are involved in the regulation of the cell cycle are mutated or over expressed. Adapted from the 2015 Cancer Product Guide, Edition 3, this poster summarizes the stages of the cell cycle and DNA repair. It also highlights strategies for enhancing replicative stress in cancer cells to force mitotic catastrophe and cell death.

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Cyclin-Dependent Kinase (Cdk) Gene Data