title: The restriction point of the cell cycle.
abstract: As formulated in 1974, the concept of the restriction point of the cell cycle was based on cell biological experiments, yet allowing accurate molecular predictions and spurring a search for the restriction factor. Although cyclin D meets the criteria of the R-factor, the picture as outlined here is more interesting and far more complex. We discuss the relationship between the restriction knot and DNA damage-checkpoints. Finally, we discuss how loss of the restriction point in cancer leads to loss of checkpoint control and to insensitivity to antimitogens including some mechanism-based anticancer therapeutics.
authors.affiliation: National Cancer Institute; National Institutes of Health; Bethesda, Maryland 20892 USA. mikhailb@mal.nih.gov
authors.forename: Mikhail V
authors.initials: MV
authors.lastname: Blagosklonny
authors.forename: Arthur B
authors.initials: AB
authors.lastname: Pardee
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D002455:Cell Division; D056741:Cyclin D; D019938:Cyclin D1 / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D016213:Cyclins / Q000378:metabolism; D025461:Feedback, Physiological; D016193:G1 Phase; D006801:Humans; D020935:MAP Kinase Signaling System; D008934:Mitogens; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D056741:Cyclin D; D019927:Cyclin E; D016213:Cyclins; D008934:Mitogens; D016271:Proto-Oncogene Proteins c-myc; D019938:Cyclin D1; D018844:Cyclin-Dependent Kinases