p14ARF tumour suppressor stabilises and activates p53 by directly interacting with (H)Mdm2 [(human) murine double minute 2 homologue] and inhibiting its E3 ubiquitin ligase activity. Here we demonstrate that p14ARF promotes accumulation of (H)Mdm2 conjugated to the small ubiquitin-like protein SUMO-1. Mutational analysis demonstrated that the N-terminus of Mdm2 is a target for p14ARF-mediated SUMO conjugation. SUMO modification requires residues 2–14 in p14ARF that interact with (H)Mdm2 and residues 82–101 in exon 2 involved in nucleolar localisation of p14ARF. These data suggest a novel role for p14ARF as a regulator of activity of (H)Mdm2, which could be related to its tumour suppressing activities.
Xirodimas, D. P., Chisholm, J., Desterro, J. M. S., Lane, D. P., Hay, R. T., & Celis, J. (Ed.) (2002). P14ARF promotes accumulation of SUMO-1 conjugated (H)Mdm2. FEBS Letters, 528(1-3), 207-211. https://doi.org/10.1016/S0014-5793(02)03310-0