Cell Cycle Control: The Restriction Point

Abstract The current understanding of the mechanism and kinetics of the G1 checkpoint called the restriction point (R‐point) in mammalian cells is discussed. The core mechanism involves a network of interactions among transcription factors (Myc and E2F) and cyclin‐dependendent kinases (CcnD/Cdk4,6 and CcnE/Cdk2). This network contains many positive feedback loops that generate a bistable switch in E2F activity which is similar to a toggle switch and explains the transition from growth‐factor‐dependent to growth‐factor‐independent transition of cell cycle progression at the R‐point. Key Concepts The restriction point (R‐point) marks the transition from growth‐factor‐dependent to growth‐factor‐independent cell cycle progression. The R‐point has been experimentally demonstrated to be governed by a bistable switch involving the transcription factor E2F. A bistable switch is similar to a toggle switch that no longer requires the initial switching stimulus once it is flipped on. The network of gene and molecular interactions that generate the R‐point switch includes several positive feedback loops among transcription factors, kinases and phosphatases.