Mdmx enhances p53 ubiquitination by altering the substrate preference of the Mdm2 ubiquitin ligase
Abstract
mdm2 and mdmx oncogenes play essential yet non-redundant roles in synergistic inactivation of the tumor suppressor, p53. While Mdm2 inhibits p53 activity mainly by augmenting its ubiquitination, the functional role of Mdmx on p53 ubiquitination remains obscure. In transfected H1299 cells, Mdmx augmented Mdm2-mediated ubiquitination of p53. In in vitro ubiquitination assays, the Mdmx/Mdm2 heteromeric complex, in comparison to the Mdm2 homomer, showed enhanced ubiquitinase activity toward p53 and the reduced auto-ubiquitination of Mdm2. Alteration of the substrate specificity via binding to Mdmx may contribute to efficient ubiquitination and inactivation of p53 by Mdm2.
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Mdm2's substrate specificity is switched from itself towards p53 upon Mdmx binding.
“By contrast, Mdm2’s substrate specificity is switched from itself towards p53 upon Mdmx binding [42].”
From The p53 orchestra: Mdm2 and Mdmx set the tone (2010) · cites this paper as [42]
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- Authors
- Okamoto, K., Taya, Y., & Nakagama, H.
- Affiliations
- Japan Science and Technology Agency (JP)
- National Cancer Center Research Institute (JP)
- Corresponding author
- Nakagama, Hitoshi
- ORCID
- Okamoto, Koji
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 2009-07-18
- Volume
- 583
- Issue
- 17
- Pages
- 2710-2714
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W2017557952
- Cited by
- 76
- References
- 38
- Citations by year
- 2024: 4 · 2022: 5 · 2021: 2 · 2020: 4 · 2019: 1 · 2017: 3 · 2016: 5 · 2015: 4 · 2014: 10 · 2013: 9 · 2012: 13
- FWCI
- 4.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (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
- MDMX, MDM2, p53, ubiquitination, E3 ubiquitin ligase, substrate specificity, p53 inactivation, tumor suppressor regulation
- MeSH terms
- Humans, Nuclear Proteins, Proto-Oncogene Proteins, Substrate Specificity, Tumor Suppressor Protein p53, Cell Cycle Proteins, Cell Line, Tumor, Proto-Oncogene Proteins c-mdm2, Ubiquitination
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