p14ARF (p19ARF in mice), which is an alternate reading frame protein product of the CDKN2A locus, mainly exerts its anti-proliferative activity via the inhibition of the mouse double minute 2 homolog (MDM2), an ubiquitin-ligase that hampers the activity of the transcription factor p53, acting as a tumor suppressor [18,19] (Figure 1). This evidence concerns the gene TP53 and neoplasm.