p300/MDM2 complexes participate in MDM2-mediated p53 degradation
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Control of p53 turnover is critical to p53 function. E1A binding to p300/CBP translates into enhanced p53 stability, implying that these coactivator proteins normally operate in p53 turnover control. In this regard, the p300 C/H1 region serves as a specific in vivo binding site for both p53 and MDM2, a naturally occurring p53 destabilizer. Moreover, most of the endogenous MDM2 is bound to p300, and genetic analysis implies that specific interactions of p53 and MDM2 with p300 C/H1 are important steps in the MDM2-directed turnover of p53. A specific role for p300 in endogenous p53 degradation is underscored by the p53-stabilizing effect of overproducing the p300 C/H1 domain. Taken together, the data indicate that specific interactions between p300/CBP C/H1, p53, and MDM2 are intimately involved in the MDM2-mediated control of p53 abundance.
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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 [87]
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- Authors
- Grossman, S. R., Perez, M., Kung, A. L., Joseph, M., Mansur, C., Xiao, Z.-X., Kumar, S., Howley, P. M., & Livingston, D. M.
- Affiliations
- Harvard University (US)
- Tufts University (US)
- Boston University (US)
- Corresponding author
- Livingston, David M
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 1998-10
- Volume
- 2
- Issue
- 4
- Pages
- 405-415
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2063877452
- Cited by
- 414
- References
- 63
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 7 · 2022: 7 · 2021: 4 · 2020: 9 · 2019: 4 · 2018: 6 · 2017: 2 · 2016: 9 · 2015: 4 · 2014: 15 · 2013: 15 · 2012: 18
- FWCI
- 19.07
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion, cc-by-nc-nd)
- 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
- P300, MDM2, p53 degradation, CBP, adenovirus E1A, protein-protein interaction, p53 stabilization, tumor suppressor regulation
- MeSH terms
- Cell Line, DNA-Binding Proteins, Humans, Molecular Sequence Data, Neoplasm Proteins, Nuclear Proteins, Oncogene Proteins, Viral, Protein Binding, Proto-Oncogene Proteins, Ubiquitins, Trans-Activators, Tumor Suppressor Protein p53, Mutagenesis, Sequence Homology, Amino Acid, Proto-Oncogene Proteins c-mdm2
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