The present invention relates to the discovery in eukaryotic cells, particularly human cells, a novel polypeptide of 16 kDa (hereinafter "p16.sup.INK4" or "p16") can function as an inhibitor of cell cycle progression, and therefore ultimately of cell growth, and that similar to the role of p21 and p53, the p16 protein may function coordinately with the cell cycle regulatory protein, retinoblastoma (Rb).