Figure 8: Model of R’s effect upon S phase entry. Unless given a signal, cells will have Rb bound to E2F to inhibit E2F activity. R protein binds to Rb, displacing it from E2F, in which case E2F will promote S phase entry. Overexpression of E2F enhances this effect. Overexpression of Rb allows for renewed E2F inhibition. p53 or p21 overexpression inhibits cell cycle progression after it is initiated by active E2F.