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
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Binding Sites
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Cell Line
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Exons
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Humans
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Macromolecular Substances
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Mice
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Nuclear Proteins*
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Proto-Oncogene Proteins / chemistry
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-mdm2
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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SUMO-1 Protein / chemistry
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SUMO-1 Protein / genetics
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SUMO-1 Protein / metabolism*
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Sequence Deletion
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Transfection
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Tumor Suppressor Protein p14ARF / chemistry
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Tumor Suppressor Protein p14ARF / genetics
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Tumor Suppressor Protein p14ARF / metabolism*
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Tumor Suppressor Protein p53 / metabolism
Substances
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Macromolecular Substances
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Nuclear Proteins
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Proto-Oncogene Proteins
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Recombinant Proteins
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SUMO-1 Protein
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Tumor Suppressor Protein p14ARF
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Tumor Suppressor Protein p53
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MDM2 protein, human
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Mdm2 protein, mouse
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Proto-Oncogene Proteins c-mdm2