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CDK6—a review of the past and a glimpse into the future: from cell-cycle control to transcriptional regulation

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Abstract

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.

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Acknowledgements

We are grateful to Peter Alexander Martinek for technical help in the generation of figures. This work was supported by the Austrian Science Foundation (FWF) via grants to VS (SFB F47 and P24297-B23).

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  1. Institute of Pharmacology and Toxicology, University of Veterinary Medicine, Vienna, Austria

    A-S Tigan, F Bellutti, K Kollmann & V Sexl

  2. Wellcome Trust/MRC Stem Cell Institute and Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK

    K Kollmann

  3. University of Veterinary Medicine, Vienna, Austria

    G Tebb

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Tigan, AS., Bellutti, F., Kollmann, K. et al. CDK6—a review of the past and a glimpse into the future: from cell-cycle control to transcriptional regulation. Oncogene 35, 3083–3091 (2016). https://doi.org/10.1038/onc.2015.407

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