The restriction point of the cell cycle.
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.
Blagosklonny
Mikhail V
MV
National Cancer Institute; National Institutes of Health; Bethesda, Maryland 20892 USA. mikhailb@mal.nih.gov
Pardee
Arthur B
AB
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
D056741:Cyclin D; D019927:Cyclin E; D016213:Cyclins; D008934:Mitogens; D016271:Proto-Oncogene Proteins c-myc; D019938:Cyclin D1; D018844:Cyclin-Dependent Kinases