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

FEBS Lett. 2002 Sep 25;528(1-3):207-11. doi: 10.1016/s0014-5793(02)03310-0.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Cell Line
  • Exons
  • Humans
  • Macromolecular Substances
  • Mice
  • Nuclear Proteins*
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-mdm2
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • SUMO-1 Protein / chemistry
  • SUMO-1 Protein / genetics
  • SUMO-1 Protein / metabolism*
  • Sequence Deletion
  • Transfection
  • Tumor Suppressor Protein p14ARF / chemistry
  • Tumor Suppressor Protein p14ARF / genetics
  • Tumor Suppressor Protein p14ARF / metabolism*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Macromolecular Substances
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Recombinant Proteins
  • SUMO-1 Protein
  • Tumor Suppressor Protein p14ARF
  • Tumor Suppressor Protein p53
  • MDM2 protein, human
  • Mdm2 protein, mouse
  • Proto-Oncogene Proteins c-mdm2