Transcriptional activator which activates the CDKN2A/ARF locus in response to Ras-Raf signaling, thereby promoting p53/TP53-dependent growth arrest. May also cooperate with MYB to activate transcription of the ANPEP gene. Binds to the consensus sequence 5'-CCCG[GT]ATGT-3'. Interacts with the D-type cyclins CCND1, CCND2 and CCND3. Interaction with D-type cyclins may modulate transcriptional activation by this protein. Ubiquitously expressed (at mRNA level). Expressed in brain, intestine, kidney, lung, pancreas, skin, spleen and tongue (at protein level). Expressed at high levels in testis and thymus (at protein level). In all tissues examined, expression is predominant in non-proliferating and differentiated cell types. These include epithelial, interstitial and smooth muscle cells of the intestine, differentiated spermatids, sperm and interstitial cells of the testis, and lymphoid cells of the medullary compartment of the thymus. Expressed throughout the cell cycle. Expression is highest in G0 and G1 phases and decreases during S and G2/M phases. Expression is induced by activation of the Ras-Raf signaling pathway, and this may require JUN and JUNB. Expression can be repressed by E2F1, E2F2, E2F3 and E2F4. Expression is also repressed by non-classical inhibitors of NF-kappa-B signaling such as doxorubicin, daunorubicin and UVC, and by the NF-kappa-B p65 subunit (RELA). Phosphorylated by the cyclin-D2/CDK4, cyclin-D3/CDK4 and cyclin-D2/CDK6 complexes and to a lesser extent by the cyclin-D1/CDK4 complex. Mice spontaneously develop tumors with a mean latency around 80 weeks. The most common tumor types are pulmonary adenomas, adenocarcinomas, hepatocellular tumors, B-cell lymphomas and vascular tumors. The protein appears to be haplo-insufficient for tumor suppression, as heterozygous animals are also prone to spontaneous tumor development. Mice lacking this protein also exhibit enhanced susceptibility to tumor induction by activated Ras or the application of dimethylbenzanthracene (DMBA) or ionizing radiation. Early passage murine embryonic fibroblasts (MEFs) from animals lacking this protein are susceptible to transformation by activated Ras alone due to functional inactivation of the ARF-p53 pathway. Late passage MEFs from animals lacking this protein escape senescence without disrupting CDKN2A/ARF or p53 function. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. Belongs to the DMTF1 family.