P14ARF promotes accumulation of SUMO-1 conjugated (H)Mdm2
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.
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Arf can stimulate Mdm2-dependent SUMOylation of itself and of p53 at K386, and SUMOylation is associated with relocalization of p53 to subnuclear structures.
“There is some consensus that Arf can stimulate the Mdm2-dependent SUMOylation of both itself and of p53 at K386 [119,120] and that SUMOylation is associated with relocalization of p53 to subnuclear structures [121,122].”
From The p53 orchestra: Mdm2 and Mdmx set the tone (2010) · cites this paper as [120]
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References 28 · Cited by 94
- Authors
- Xirodimas, D. P., Chisholm, J., Desterro, J. M. S., Lane, D. P., & Hay, R. T.
- Affiliations
- University of Dundee (GB)
- University of St Andrews (GB)
- Corresponding author
- Hay, Ronald T
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 2002-08-30
- Volume
- 528
- Issue
- 1-3
- Pages
- 207-211
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W1983055012
- Cited by
- 94
- References
- 28
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 1 · 2019: 1 · 2018: 5 · 2016: 1 · 2015: 4 · 2014: 4 · 2013: 6 · 2012: 4
- FWCI
- 3.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion)
- HAL (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Keywords
- p14ARF, MDM2, SUMOylation, p53, tumour suppressor, E3 ubiquitin ligase, protein stability
- MeSH terms
- Animals, Binding Sites, Cell Line, Exons, Humans, Nuclear Proteins, Proto-Oncogene Proteins, Recombinant Proteins, Transfection, Tumor Suppressor Protein p53, Sequence Deletion, Tumor Suppressor Protein p14ARF, SUMO-1 Protein, Macromolecular Substances, Mice, Proto-Oncogene Proteins c-mdm2
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