p16-INK4a is a nuclear protein that regulates the cell cycle by inhibiting cyclin dependent kinase-4 (CDK4) and CDK6. p16-INK4a inhibits CDK activity by binding to the CDK molecules in a manner that interferes with their ability to interact with cyclin D. This activity has the effect of suppressing tumor formation and growth, and of inducing replicative senescence in various normal cells, including stem cells. The expression of p16-INK4a steadily increases with age and tends to accumulate in stem cell compartments. The deletion, rearrangement, or mutation of the p16-INK4a gene is frequently found in melanomas as well as in certain other types of cancer. Recombinant p16-INK4a is a 16.5 kDa protein containing 156 amino acid residues. Kim, W.Y. and Sharpless, N.E. (2006) Cell 127(2):265-75.