p16INK4a is a negative regulator of CDK4 and CDK6 kinase activity and cell cycle progression. p16INK4a regulates the cell cycle by inhibiting cyclin/CDK complex formation and the phosphorylation of the retinoblastoma protein (pRb). The gene which encodes p16INK4a, CDKN2A, is frequently mutated or deleted in a wide variety of tumors and is known to be an important tumor suppressor gene. The CDKN2A gene also generates a distinct transcript variant and protein, p14ARF, from an alternate open reading frame (ARF).
