p14ARF/CDKN2A Products

P14ARF is an alternate reading frame (ARF) product of the CDKN2A locus, which acts as a tumor suppressor by inducing cell cycle arrest in G1 and G2 phases and apoptosis.

The INK4a-ARF locus is comprised of two tumor suppressors, p16INK4a and p14ARF. These two proteins are encoded by differential splicing of alternative first exons. The p16INK4a (exon 1 alpha) protein inhibits the cyclin D-dependent kinases (CDK) that control the phosphorylation of the Rb protein and cell proliferation. The p14ARF protein complexes with MDM2 within the nucleus, thus modulating the activity of the p53 protein. P14ARF is a potent tumor suppressor in the presence of wild-type p53, while mutant p53 substantially reduces growth inhibition by p14ARF.