| abstract |
(57) [Summary]nThe INK4A (MTS1, CDKN2) gene encodes a specific inhibitor of the cyclin D-dependent kinases CDK4 and CDK6 (InK4a-p16). InK4a-p16 blocks these kinases from phosphorylating the retinoblastoma protein pRb and prevents them from exiting the G1 phase of the cell cycle. Deletions and mutations involving the genes encoding InK4a-p16, INK4A occur frequently in cancer cells, suggesting that INK4a-p16, like pRb, suppresses tumorigenesis. However, a completely unrelated protein (ARF-p19) occurs in a major part from another reading frame of the mouse INK4A gene. Expression of ARF-p19 cDNA (SEQ ID NO: 1) in rodent fibroblasts induces both G1 and G2 phase arrest. Economic reuse of protein-coding sequences in this manner has not previously existed in the mammalian genome, and the single genetics of INK4a-p16 and ARF-p19 have both been involved in cell cycle control. It may reflect a dual requirement for protein. |