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Concept
Cyclin-dependent kinase 6
Summary
Cell division protein kinase 6 (CDK6) is an enzyme encoded by the CDK6 gene. It is regulated by cyclins, more specifically by Cyclin D proteins and Cyclin-dependent kinase inhibitor proteins. The protein encoded by this gene is a member of the cyclin-dependent kinase, (CDK) family, which includes CDK4. CDK family members are highly similar to the gene products of Saccharomyces cerevisiae cdc28, and Schizosaccharomyces pombe cdc2, and are known to be important regulators of cell cycle progression in the point of regulation named R or restriction point.
This kinase is a catalytic subunit of the protein kinase complex, important for the G1 phase progression and G1/S transition of the cell cycle and the complex is composed also by an activating sub-unit; the cyclin D. The activity of this kinase first appears in mid-G1 phase, which is controlled by the regulatory subunits including D-type cyclins and members of INK4 family of CDK inhibitors. This kinase, as well as CDK4, has been shown to phosphorylate, and thus regulate the activity of, tumor suppressor Retinoblastoma protein making CDK6 an important protein in cancer development.
The CDK6 gene is conserved in eukaryotes, including the budding yeast and the nematode Caenorhabditis elegans. The CDK6 gene is located on chromosome 7 in humans. The gene spans 231,706 base pairs and encodes a 326 amino acid protein with a kinase function. The gene is overexpressed in cancers like lymphoma, leukemia, medulloblastoma and melanoma associated with chromosomal rearrangements.
The CDK6 protein contains a catalytic core composed of a serine/threonine domain. This protein also contains an ATP-binding pocket, inhibitory and activating phosphorylation sites, a PSTAIRE-like cyclin-binding domain and an activating T-loop motif. After binding the Cyclin in the PSTAIRE helix, the protein changes its conformational structure to expose the phosphorylation motif. The protein can be found in the cytoplasm and the nucleus, however most of the active complexes are found in the nucleus of proliferating cells.
Official source
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