G1/S cell cycle transition in normal and tumoral cells.

G1/S transition in normal cells is regulated by Rb phosphorylation by cyclin D/CDK4 and cyclin E/CDK2 complexes. In tumoral B cells, inactivation of p53 leading to absence of p21^CIP1 or loss of p16^INK4a both lead to increased Rb phosphorylation and consequent release of E2F transcription factors. Inactivation of p27^KIP1 by increase in its degradation or by sequestration in cyclin D/CDK4 complexes also stimulates Rb phosphorylation by cyclin E/CDK2. K2, CDK2; K4, CDK4; E, cyclin E; D, cyclin D; Ub, ubiquitin.