p16INK4a inhibits cyclin-dependent kinase 4 (CDK4) and CDK6, preventing phosphorylation of the retinoblastoma protein (Rb), a key regulator of the cell cycle transition from the G1 phase to the S phase. By controlling this checkpoint, p16INK4a ensures that cells do not proliferate unchecked. On the other hand, p14ARF stabilizes the p53 tumor suppressor protein by inhibiting MDM2, a protein that promotes p53 degradation.
