P14ARF promotes accumulation of SUMO-1 conjugated (H)Mdm2

D P Xirodimas, J Chisholm, J M S Desterro, D P Lane, R T Hay

Research output: Contribution to journalArticlepeer-review

81 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)207-211
Number of pages5
JournalFEBS Letters
Volume528
DOIs
Publication statusPublished - 25 Sept 2002

Keywords

  • (H)Mdm2
  • p14ARF
  • SUMO conjugation
  • TUMOR-SUPPRESSOR P53
  • UBIQUITIN LIGASE
  • IN-VIVO
  • NUCLEOLAR LOCALIZATION
  • EMBRYONIC LETHALITY
  • MDM2-DEFICIENT MICE
  • MDM2
  • PROTEIN
  • P19(ARF)
  • P14(ARF)

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