Stabilization of p53 by p14(ARF) without relocation of MDM2 to the nucleolus

The alternative product of the human INK4a/ARF locus, p14(ARF), has the pot ential to act as a tumour suppressor by binding to and inhibiting the p53 a ntagonist MDM2. Current models propose that ARF function depends on its abi lity to sequester MDM2 in the nucleolus. Here we describe situations in whi ch stabilization of MDM2 and p53 occur without relocalization of endogenous MDM2 from the nucleoplasm. Conversely, forms of Apr that do not accumulate in the nucleolus retain the capacity to stabilize MDM2 and p53. We therefo re propose that nucleolar localization is not essential for ARF function bu t may enhance the availability of ARF to inhibit MDM2.