Review Volume 3, Issue 6 pp 565—575

Figure 2. Effects of p16^Ink4a on Cdk4/6. (A) The p16^Ink4a cell cycle inhibitor sequesters Cdk4 or Cdk6, preventing interactions with cyclin D proteins, and thus phosphorylation of pRB. Hypophosphorylated pRB sequesters the E2F transcription factor, thus thus inihibiting cell cycle progression. (B) In the absence of p16^Ink4a, cyclin D forms a productive complex with either Cdk4 or Cdk6 and phosphorylates RB. This phosphorylation releases the E2F transcription factor, facilitating the G1 to S phase cell cycle transition. Thus, in the presence of elevated p16^Ink4a, such as with aging, there is cell cycle arrest and cellular senescence. Adapted from [32]