The Cell Cycle: a Review of Regulation, Deregulation and Therapeutic Targets in Cancer

Overview

Journal Cell Prolif

Date 2003 Jun 20

PMID 12814430

Citations 614

Authors

Katrien Vermeulen

Dirk R Van Bockstaele

Zwi N Berneman

Affiliations

Soon will be listed here.

Abstract

The cell cycle is controlled by numerous mechanisms ensuring correct cell division. This review will focus on these mechanisms, i.e. regulation of cyclin-dependent kinases (CDK) by cyclins, CDK inhibitors and phosphorylating events. The quality checkpoints activated after DNA damage are also discussed. The complexity of the regulation of the cell cycle is also reflected in the different alterations leading to aberrant cell proliferation and development of cancer. Consequently, targeting the cell cycle in general and CDK in particular presents unique opportunities for drug discovery. This review provides an overview of deregulation of the cell cycle in cancer. Different families of known CDK inhibitors acting by ATP competition are also discussed. Currently, at least three compounds with CDK inhibitory activity (flavopiridol, UCN-01, roscovitine) have entered clinical trials.

Citing Articles

Polyethylene Glycolylation of the Purified Basic Protein (Protamine) of Squid (): Structural Changes and Evaluation of Proliferative Effects on Fibroblast.

Li N, Xu J, Li Y, Elango J, Wu W Int J Mol Sci. 2025; 26(5).

PMID: 40076495 PMC: 11899872. DOI: 10.3390/ijms26051869.

Reversible and effective cell cycle synchronization method for studying stage-specific processes.

Chen Y, Reddy S, Suzuki A Life Sci Alliance. 2025; 8(5).

PMID: 40037894 PMC: 11880160. DOI: 10.26508/lsa.202403000.

Impact of G1 phase kinetics on the acquisition of stemness in cancer cells: the critical role of cyclin D.

Ahmadi Y, Faiq T, Abolhasani S Mol Biol Rep. 2025; 52(1):230.

PMID: 39951181 DOI: 10.1007/s11033-025-10351-3.

Inotodiol induces hepatocellular carcinoma apoptosis by activation of MAPK/ERK pathway.

Xing Y, Jia D, Zhu X, Yang J, Gao Z, Meng N PLoS One. 2025; 20(1):e0318450.

PMID: 39879230 PMC: 11778785. DOI: 10.1371/journal.pone.0318450.

In vitro antitumor effects of methanolic extracts of three Ganoderema mushrooms.

Toson E, El-Fallal A, Oransa M, El-Gharabawy H Sci Rep. 2025; 15(1):2274.

PMID: 39824924 PMC: 11748650. DOI: 10.1038/s41598-025-86162-0.

References

Kamb A . Cyclin-dependent kinase inhibitors and human cancer. Curr Top Microbiol Immunol. 1998; 227:139-48. DOI: 10.1007/978-3-642-71941-7_7. View

Evans T, Rosenthal E, Youngblom J, Distel D, Hunt T . Cyclin: a protein specified by maternal mRNA in sea urchin eggs that is destroyed at each cleavage division. Cell. 1983; 33(2):389-96. DOI: 10.1016/0092-8674(83)90420-8. View

MORGAN D . Principles of CDK regulation. Nature. 1995; 374(6518):131-4. DOI: 10.1038/374131a0. View

Gronbaek K, Nedergaard T, Andersen M, Thor Straten P, Guldberg P, Moller P . Concurrent disruption of cell cycle associated genes in mantle cell lymphoma: a genotypic and phenotypic study of cyclin D1, p16, p15, p53 and pRb. Leukemia. 1998; 12(8):1266-71. DOI: 10.1038/sj.leu.2401090. View

Fang G, Yu H, Kirschner M . The checkpoint protein MAD2 and the mitotic regulator CDC20 form a ternary complex with the anaphase-promoting complex to control anaphase initiation. Genes Dev. 1998; 12(12):1871-83. PMC: 316912. DOI: 10.1101/gad.12.12.1871. View

Lew D, Kornbluth S . Regulatory roles of cyclin dependent kinase phosphorylation in cell cycle control. Curr Opin Cell Biol. 1996; 8(6):795-804. DOI: 10.1016/s0955-0674(96)80080-9. View

Bojanowski K, Nishio K, Fukuda M, Larsen A, Saijo N . Effect of suramin on p34cdc2 kinase in vitro and in extracts from human H69 cells: evidence for a double mechanism of action. Biochem Biophys Res Commun. 1994; 203(3):1574-80. DOI: 10.1006/bbrc.1994.2366. View

Easton J, Wei T, Lahti J, Kidd V . Disruption of the cyclin D/cyclin-dependent kinase/INK4/retinoblastoma protein regulatory pathway in human neuroblastoma. Cancer Res. 1998; 58(12):2624-32. View

Hunter T, Pines J . Cyclins and cancer. II: Cyclin D and CDK inhibitors come of age. Cell. 1994; 79(4):573-82. DOI: 10.1016/0092-8674(94)90543-6. View

10.

Hoffmann I, Clarke P, Marcote M, Karsenti E, Draetta G . Phosphorylation and activation of human cdc25-C by cdc2--cyclin B and its involvement in the self-amplification of MPF at mitosis. EMBO J. 1993; 12(1):53-63. PMC: 413175. DOI: 10.1002/j.1460-2075.1993.tb05631.x. View

11.

Pines J . Cyclins and cyclin-dependent kinases: theme and variations. Adv Cancer Res. 1995; 66:181-212. DOI: 10.1016/s0065-230x(08)60254-7. View

12.

Lee M, Reynisdottir I, Massague J . Cloning of p57KIP2, a cyclin-dependent kinase inhibitor with unique domain structure and tissue distribution. Genes Dev. 1995; 9(6):639-49. DOI: 10.1101/gad.9.6.639. View

13.

Hengst L, Reed S . Inhibitors of the Cip/Kip family. Curr Top Microbiol Immunol. 1998; 227:25-41. DOI: 10.1007/978-3-642-71941-7_2. View

14.

Crook T, Vousden K . Interaction of HPV E6 with p53 and associated proteins. Biochem Soc Trans. 1994; 22(1):52-5. DOI: 10.1042/bst0220052. View

15.

Jeffrey P, Russo A, Polyak K, Gibbs E, Hurwitz J, Massague J . Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex. Nature. 1995; 376(6538):313-20. DOI: 10.1038/376313a0. View

16.

Moller M, Ino Y, Gerdes A, Skjodt K, Louis D, Pedersen N . Aberrations of the p53 pathway components p53, MDM2 and CDKN2A appear independent in diffuse large B cell lymphoma. Leukemia. 1999; 13(3):453-9. DOI: 10.1038/sj.leu.2401315. View

17.

Kaur G, Stetler-Stevenson M, Sebers S, Worland P, Sedlacek H, Myers C . Growth inhibition with reversible cell cycle arrest of carcinoma cells by flavone L86-8275. J Natl Cancer Inst. 1992; 84(22):1736-40. DOI: 10.1093/jnci/84.22.1736. View

18.

Bradbury E, Inglis R, Matthews H . Control of cell division by very lysine rich histone (F1) phosphorylation. Nature. 1974; 247(5439):257-61. DOI: 10.1038/247257a0. View

19.

Gadbois D, Hamaguchi J, Swank R, Bradbury E . Staurosporine is a potent inhibitor of p34cdc2 and p34cdc2-like kinases. Biochem Biophys Res Commun. 1992; 184(1):80-5. DOI: 10.1016/0006-291x(92)91160-r. View

20.

Horsthemke B . Genetics and cytogenetics of retinoblastoma. Cancer Genet Cytogenet. 1992; 63(1):1-7. DOI: 10.1016/0165-4608(92)90055-d. View