Checkpoint genes in cancer.
The mammalian cell cycle is exquisitely controlled by a 'machinery' composed of cyclin-dependent kinases and their binding partners, the cyclins. These kinases regulate transitions into DNA synthesis and mitosis, and their inactivity contributes to cellular quiescence, differentiation and senescence. Cell cycle transitions are, in turn, controlled by checkpoints that monitor ribonucleotide pools, oxygen tension, the extracellular environment, growth signalling programmes, the status of DNA replication, and the mitotic spindle apparatus. Genes positively controlling cell cycle checkpoints can be targets for oncogenic activation in cancer, whereas negative regulators, such as tumour suppressor genes, are targeted for inactivation. Understanding the molecular details of cell cycle regulation and checkpoint abnormalities in cancer offers insight into potential therapeutic strategies.
McDonald
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Department of Medicine, Genetics and Pharmacology, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
El-Deiry
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D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors / Q000235:genetics*; D019925:Cyclin A / Q000235:genetics; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins / Q000235:genetics; D004249:DNA Damage / Q000235:genetics; D018816:Genes, cdc / Q000502:physiology*; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D008938:Mitosis / Q000235:genetics; D016296:Mutagenesis / Q000235:genetics; D009369:Neoplasms / Q000235:genetics*; D010766:Phosphorylation
C534702:CCNG1 protein, human; D019925:Cyclin A; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins; D016203:CDC2 Protein Kinase