MDM2-ARF complex regulates p53 sumoylation
Abstract
The p53 tumor suppressor is regulated by MDM2-mediated ubiquitination and degradation. Ubiquitination of p53 is regulated by ARF, which binds to MDM2 and inhibits its E3 ligase function. P53 is also subjected to modification by conjugation of SUMO-1. We found that a p53 mutant deficient for MDM2 binding (p53(14Q19S)) is poorly sumoylated in vivo compared to wild-type p53. Overexpression of MDM2 increases the level of p53 sumoylation, which is further stimulated by expression of ARF. Stimulation of p53 sumoylation requires a highly conserved region (102-116) encoded by exon 2 of ARF and correlates with the ability of ARF to target p53 to the nucleolus. An MDM2 deletion mutant (MDM2(Delta222-437)) with activated cryptic nucleolar localization signal also targets p53 to the nucleolus and efficiently promotes p53 sumoylation in the absence of ARF. Direct targeting of p53 to the nucleolus enhances its sumoylation in an MDM2- and ARF-dependent fashion. These results show that p53 sumoylation is regulated by MDM2- and ARF-mediated nucleolar targeting.
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Mdm2 can also mediate p53 SUMOylation.
“Other reports indicate Mdm2 can also fulfill this role [119].”
From The p53 orchestra: Mdm2 and Mdmx set the tone (2010) · cites this paper as [119]
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 [119]
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- Authors
- Chen, L., & Chen, J.
- Affiliations
- Moffitt Cancer Center (US)
- Corresponding author
- Chen, Jiandong
- Venue
- Oncogene
- Published
- 2003-08-14
- Volume
- 22
- Issue
- 34
- Pages
- 5348-5357
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2063060712
- Cited by
- 134
- References
- 30
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 4 · 2022: 16 · 2021: 7 · 2020: 4 · 2019: 2 · 2018: 6 · 2017: 2 · 2016: 5 · 2015: 3 · 2014: 6 · 2013: 8 · 2012: 3
- FWCI
- 3.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Cancer Society
- National Institutes of Health
- 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
- p53, MDM2, ARF, SUMO1, nucleolar targeting, nucleolar localization signal, p53 ubiquitination, E3 ubiquitin ligase, tumor suppressor regulation
- MeSH terms
- Cell Nucleolus, Cysteine Endopeptidases, Humans, Lysine, Mutation, Nuclear Proteins, Endopeptidases, Protein Binding, Proto-Oncogene Proteins, Tumor Cells, Cultured, Tumor Suppressor Protein p53, ADP-Ribosylation Factors, Proto-Oncogene Proteins c-mdm2
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