Figure 1

Relationship between Rb brake and other aspects of cell cycle. The Rb protein acts as a brake on several of the phases of the cell cycle, dependent upon its state of phosphorylation. In the hyperphosphorylated state, the Rb brake is inactive, permitting the transcription factors to become activated and cellular proliferation to proceed. During this period the ratio [GSSG]/[GSH] is low and E falls below θ. The cell passes through the restriction point R to the later stage of G₁, termed G_1ps, on to S, from which it passes through G₂ to the early M phase. After mid-M, the Rb protein becomes hypophosphylated and the brake is active. The transcription factors are inactivated and cell proliferation is stopped. During this period the ratio [GSSG]/[GSH] is high and E rises above θ. The cell passes through M to the early stage of G₁, termed G_1pm, from which it may either return to the cell cycle via R or it passes into a resting stage, G₀. In cancer, a portion of the cycle can be short-circuited, via the M to G_1ps bypass. R = site of restriction point. Arrow with interrupted line represents short-circuit in cancer. θ = -207 ± 11 mV.