Historical Background: Cyclin-Dependent Kinase 4 (CDK4) in Cell Cycle Control and Regulation
The mammalian cell cycle is typically divided into four phases, G1, S, G2, and M, and within the last two decades, there have been a series of discoveries that have provided us with a better understanding of the control mechanisms that regulate cell cycle progression. It is apparent that the order and timing of the cell cycle is critical for accurate transmission of genetic information, and consequently, a number of biochemical pathways have evolved to ensure that initiation of a particular cell cycle event is dependent on the accurate completion of another. These biochemical pathways have been termed “checkpoints.”
Mitogenic growth factors bind to their cognate receptors and initiate a cascade of events that culminate in the expression and assembly of different kinase holoenzymes composed of a regulatory subunit,...
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References
Baker SJ, Reddy EP. CDK4: a key player in the cell cycle, development, and cancer. Genes Cancer. 2012;3:658–69.
Blain SW. Switching cyclin D-Cdk4 kinase activity on and off. Cell Cycle. 2008;7:892–8.
Buckley MF, Sweeney KJ, Hamilton JA, et al. Expression and amplification of cyclin genes in human breast cancer. Oncogene. 1993;8:2127–33.
Connell-Crowley L, Harper JW, Goodrich DW. Cyclin D1/Cdk4 regulates retinoblastoma protein-mediated cell cycle arrest by site-specific phosphorylation. Mol Biol Cell. 1997;8:287–301.
Denicourt C, Dowdy SF. Cip/Kip proteins: more than just CDKs inhibitors. Genes Dev. 2004;18:851–5.
Endicott J, Noble ME, Tucker JA. Cyclin-dependent kinases: inhibition and substrate recognition. Curr Opin Struct Biol. 1999;9:738–44.
Fry DW, Harvey PJ, Keller PR, et al. Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. Mol Cancer Ther. 2004;3:1427–38.
Gil J, Peters G. Regulation of the INK4b-Arf-INK4a tumor suppressor locus: all for one and one for all. Nat Rev Mol Cell Biol. 2006;7:667–77.
Grafstrom RH, Pan W, Hoess RH. Defining the substrate specificity of cdk4 kinase-cyclin D1 complex. Carcinogenesis. 1999;202:193–8.
Harbour JW, Dean DC. The Rb/E2F pathway: expanding roles and emerging paradigms. Genes Dev. 2000;14:2393–409.
Kato JY, Matsuoka M, Strom DK, Sherr CJ. Regulation of cyclin D-dependent kinase 4 (cdk4) by cdk4-activating kinase. Mol Cell Biol. 1994;14:2713–21.
Kitagawa M, Higashi H, Jung HK, et al. The consensus motif for phosphorylation by cyclin D1-Cdk4 is different from that for phosphorylation by cyclin A/E-Cdk2. EMBO J. 1996;15:7060–9.
Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer. 2009;9:153–66.
Morgan DO. Cyclin-dependent kinases: engines, clocks, and microprocessors. Ann Rev Cell Dev Biol. 1997;13:261–91.
Rane SG, Dubus PD, Mettus RV, et al. Loss of cyclin-dependent kinase 4 expression causes infertility and insulin-dependent diabetes while its activation results in pancreatic islet hyperplasia. Nat Gen. 1999;22:44–52.
Takaki T, Echalier A, Brown NR, Hunt T, Endicott JA, Noble ME. The structure of CDK4/cyclin D3 has implications for models of CDK activation. Proc Natl Acad Sci USA. 2009;106:4171–6.
Toogood PL, Harvey PJ, Repine JT, et al. Discovery of a potent and selective inhibitor of cyclin-dependent kinase 4/6. J Med Chem. 2005;48:2388–406.
VanArsdale T, Boshoff C, Arndt KT, Abraham RT. Molecular Pathways: targeting the cyclin D-CDK4/6 axis for cancer treatment. Clin Cancer Res. 2015;21:2905–10.
Wolfel T, Hauer M, Schneider J, et al. A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma. Science. 1995;269:1281–4.
Zuo L, Weger J, Yang Q, et al. Germline mutations in the p16INK4a binding domain of CDK4 in familial melanoma. Nat Genet. 1996;12:97–9.
Acknowledgments
This work was supported by grants from the NIH (P01CA-130821), (NIH-RO1-CA-158209) to EPR.
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The authors declare no conflicts of interest with respect to the authorship and publication of this article.
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Baker, S.J., Premkumar Reddy, E. (2018). CDK4. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_101949
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