MDMX inhibits the p300/CBP-mediated acetylation of p53
Abstract
The p300/CBP-mediated acetylation of p53 significantly potentiates p53-mediated transactivation and growth inhibition. MDM2 inhibits the acetylation of p53 by p300/CBP through a mechanism that requires a stable p53-MDM2 interaction and that is sensitive to the deacetylase inhibitor, TSA. MDMX is an MDM2-like protein that shares with MDM2 the ability to interact with p53 and, in turn, inhibit p53-mediated transcription. It was therefore of interest to determine if MDMX could also inhibit the acetylation of p53 by p300/CBP. We demonstrate that MDMX dramatically inhibits the acetylation of p53 induced by both endogenous and ectopically expressed p300/CBP. We also demonstrate that the p53-binding domain of MDMX is required for the MDMX-mediated inhibition of p53 acetylation. Our results indicate that MDMX shares with MDM2 the ability to regulate a potentially important post-translational modification of p53. These results may have important biologic implications with respect to the MDMX-mediated regulation of p53 activity during development.
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Mdm2 and Mdmx bind many other proteins, including proteins involved in development, morphogenesis, and tumorigenesis.
“However, both Mdm2 and Mdmx interact with many other proteins, including those involved in development, morphogenesis and tumorigenesis (Table 2; [81–92]).”
From The p53 orchestra: Mdm2 and Mdmx set the tone (2010) · cites this paper as [84]
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MDM4 at the Crossroads: Beyond p53 and MDM2
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- Authors
- Sabbatini, P., & McCormick, F.
- Affiliations
- University of California, San Francisco (US)
- Venue
- DNA and Cell Biology
- Publisher
- SAGE Publications
- Published
- 2002-07
- Volume
- 21
- Issue
- 7
- Pages
- 519-525
- ISSN
- 1044-5498 (ISSN-L)
- 1557-7430
- OpenAlex
- W1983939040
- Cited by
- 62
- References
- 49
- Citations by year
- 2026: 1 · 2024: 1 · 2022: 1 · 2021: 3 · 2020: 1 · 2018: 4 · 2017: 3 · 2016: 6 · 2015: 3 · 2014: 4 · 2012: 3
- FWCI
- 1.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- DNA and Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- MDMX, P300, CBP, p53 acetylation, p53-MDM2 interaction, p53 transactivation, histone deacetylase inhibition, trichostatin A, p53-binding domain
- MeSH terms
- Acetylation, Animals, Binding Sites, Cell Line, DNA-Binding Proteins, Humans, Models, Biological, Nuclear Proteins, Protein Processing, Post-Translational, Proto-Oncogene Proteins, Recombinant Proteins, Transfection, Trans-Activators, Tumor Suppressor Protein p53, Protein Serine-Threonine Kinases, Protein Structure, Tertiary, Mice, Knockout, E1A-Associated p300 Protein, Mice, Proto-Oncogene Proteins c-mdm2, DNA-Activated Protein Kinase
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