p14ARF

p14^ARF, encoded by the CDKN2A locus, is a tumor suppressor that binds MDM2, the ubiquitin ligase that degrades p53, and holds it in the nucleolus.

Function

ARF responds to hyperproliferative signals - oncogene activation, E2F overactivity - rather than to DNA damage. Activated ARF binds MDM2 in the nucleolus, holding it away from p53; p53 stabilizes and accumulates, and the cell arrests or dies. DNA damage signals through ATM to p53, while oncogene activation signals through ARF to p53, so a cell faces p53-mediated arrest whether its genome is damaged or its growth signaling is activated by an oncogene. The mouse homolog, p19^ARF, serves the same