Cell Cycle · 2002 · 406 citations · 0 references
Life SciencesCell BiologyMolecular BiologyCell CycleMolecular OncologyOncogenesCell Cycle ControlCell Cycle SignalingCell-cycle CheckpointsCell-cycle DysregulationCell-cycle RegulationCyclin-dependent KinasesCell Cycle DynamicsCyclin D RegulationCyclin RegulationDna Damage ResponsesGrowth FactorsGrowth Restriction FactorMitotic Checkpoint ControlRestriction Point Regulation
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.