P14ARF promotes accumulation of SUMO-1 conjugated (H)Mdm2.
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.
Mesh Terms:
Animals, Binding Sites, Cell Line, Exons, Humans, Macromolecular Substances, Mice, Nuclear Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-mdm2, Recombinant Proteins, SUMO-1 Protein, Sequence Deletion, Transfection, Tumor Suppressor Protein p14ARF, Tumor Suppressor Protein p53
Animals, Binding Sites, Cell Line, Exons, Humans, Macromolecular Substances, Mice, Nuclear Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-mdm2, Recombinant Proteins, SUMO-1 Protein, Sequence Deletion, Transfection, Tumor Suppressor Protein p14ARF, Tumor Suppressor Protein p53
FEBS Lett.
Date: Sep. 25, 2002
PubMed ID: 12297306
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