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Infrequent epigenetic dysregulation of CIP/KIP family of cyclin-dependent kinase inhibitors in multiple myeloma

Leukemia volume 19, pages 2352–2355 (2005)Cite this article

TO THE EDITOR

Cell cycle progression is triggered by the activation of cyclin-dependent kinase 4/6 (CDK4/6) upon binding of cyclin D, and further potentiated by subsequent activation of CDK2. On the other hand, the cell cycle is negatively regulated by the INK4 (p15, p16, p18 and p19) and the CIP/KIP (p21CIP, p27KIP1and p57KIP2) families of cyclin-dependent kinase inhibitors (CKI).1 The INK4 family of CKIs bind to and inhibit CDK4/6.2 By contrast, the CKIs of the CIP/KIP family may bind to both CDK2 and CDK4/6, and modulate their kinase activities. In quiescent cells, CIP/KIP CKIs bind to and inhibit the activity of CDK2, resulting in cell cycle arrest. In cycling cells, CKIs of the CIP/KIP family detach from CDK2/cyclin E complex and bind to CDK4/6 instead, resulting in derepression (and thus activation) of CDK2 and further activation of CDK4/6, resulting in commitment of the cell to transit the G1S cell cycle checkpoint.1

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Acknowledgements

We thank Dr Andrew Zannettino, Myeloma and Mesenchymal Research Laboratory, Division of Haematology, Institute of Medical and Veterinary Science, and Hanson Institute, Adelaide, Australia, for the six cell lines. We also thank Miss YY Chan and her team for the excellent nursing care of the patients.

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  1. Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong

    C S Chim, R Liang, T K Fung & Y L Kwong

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  1. C S Chim
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Correspondence to C S Chim or Y L Kwong.

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Chim, C., Liang, R., Fung, T. et al. Infrequent epigenetic dysregulation of CIP/KIP family of cyclin-dependent kinase inhibitors in multiple myeloma. Leukemia 19, 2352–2355 (2005). https://doi.org/10.1038/sj.leu.2403904

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