CDK6-a review of the past and a glimpse into the future: from cell-cycle control to transcriptional regulation.
The G1 cell-cycle kinase CDK6 has long been thought of as a redundant homolog of CDK4. Although the two kinases have very similar roles in cell-cycle progression, it has recently become apparent that they differ in tissue-specific functions and contribute differently to tumor development. CDK6 is directly involved in transcription in tumor cells and in hematopoietic stem cells. These functions point to a role of CDK6 in tissue homeostasis and differentiation that is partially independent of CDK6's kinase activity and is not shared with CDK4. We review the literature on the contribution of CDK6 to transcription in an attempt to link the new findings on CDK6's transcriptional activity to cell-cycle progression. Finally, we note that anticancer therapies based on the inhibition of CDK6 kinase activity fail to take into account its kinase-independent role in tumor development.
Institute of Pharmacology and Toxicology, University of Veterinary Medicine, Vienna, Austria.
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Tigan
Institute of Pharmacology and Toxicology, University of Veterinary Medicine, Vienna, Austria.
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F
Bellutti
Institute of Pharmacology and Toxicology, University of Veterinary Medicine, Vienna, Austria.|Cambridge Institute for Medical Research, Wellcome Trust/MRC Stem Cell Institute and Department of Haematology, University of Cambridge, Cambridge, UK.
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Kollmann
University of Veterinary Medicine, Vienna, Austria.
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Tebb
Institute of Pharmacology and Toxicology, University of Veterinary Medicine, Vienna, Austria.
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Sexl
D059447:Cell Cycle Checkpoints / Q000235:genetics; D051361:Cyclin-Dependent Kinase 6 / Q000235:genetics* / Q000378:metabolism*; D015533:Transcriptional Activation
C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6