Journal
FEBS LETTERS
Volume 528, Issue 1-3, Pages 207-211Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0014-5793(02)03310-0
Keywords
(H)Mdm2; p14ARF; SUMO conjugation
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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. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.
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