{"type":"root","children":[{"type":"paragraph","children":[{"type":"text","value":"ARF tumor suppressor (p14ARF or ARF) encoded by the p16 tumor suppressor gene is an alternate reading frame protein product of the CDKN2A locus (INK4a/ARF). p14ARF accumulates mainly in the nucleolus where it forms stable complexes with nucleophosmin (NPM) or mouse double minute 2 homolog (MDM2). These interactions allow p14ARF to act as a tumor suppressor by inhibiting ribosomebiogenesis or initiating p53-dependent cell cycle arrest and apoptosis, respectively. Both p16INK4a and p14ARF are involved in cell cycle regulation. p14ARF inhibits MDM2, thus promoting p53, which promotes p21 activation, which then binds and inactivates certain cyclin-CDK complexes, which would otherwise promote transcription of genes that would carry the cell through the G1/S checkpoint of the cell cycle. Loss of p14ARF by a homozygous mutation in the CDKN2A gene will lead to elevated levels of MDM2 and, therefore, loss of p53 function and cell cycle control. Defects in p14ARF orCDKN2A locus are associated with the clinicopathological features of different cancers."}]}]}