Mdm2 binds p73α without targeting degradation
Abstract
The function of the p53 tumor suppressor protein is regulated by interaction with Mdm2, which targets p53 for ubiquitin dependent degradation. We show here that like p53, p73 alpha forms an interaction with Mdm2, both in vitro and in cells, but this does not result in the degradation of the p73 alpha protein. The human papillomavirus E6 protein also fails to degrade p73 alpha, suggesting that the mechanisms governing p73 alpha stability are distinct from those known to regulate p53 stability. However, the interaction of Mdm2 with 73 alpha is sufficient to impede p73 alpha transcriptional function, despite the lack of degradation.
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Mdm2 does not ubiquitinate p73α.
“While p53 and p73α can both interact with Mdm2 in the same N-terminal hydrophobic pocket (12), Mdm2 does not ubiquitinate p73α (44–46).”
From Potentiation of carboplatin-mediated DNA damage by the Mdm2 modulator Nutlin-3a in a humanized orthotopic breast-to-lung metastatic model (2015) · cites this paper as [46]
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- Authors
- Bálint, E., Bates, S., & Vousden, K. H.
- ORCID
- Vousden, Karen H
- Venue
- Oncogene
- Published
- 1999-07-08
- Volume
- 18
- Issue
- 27
- Pages
- 3923-3929
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2340120319
- Cited by
- 212
- References
- 24
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 4 · 2022: 5 · 2021: 7 · 2020: 4 · 2019: 6 · 2018: 2 · 2017: 4 · 2016: 4 · 2015: 11 · 2014: 7 · 2013: 8 · 2012: 5
- FWCI
- 7.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute
- 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
- MDM2, p53, protein-protein interaction, protein stability, ubiquitin-mediated proteolysis, E6 oncoprotein, transcriptional repression, tumor suppressor regulation
- MeSH terms
- Tumor Protein p73, Amino Acid Sequence, Cysteine Endopeptidases, DNA-Binding Proteins, Humans, Molecular Sequence Data, Multienzyme Complexes, Nuclear Proteins, Oncogene Proteins, Viral, Proto-Oncogene Proteins, Repressor Proteins, Osteosarcoma, Transcription, Genetic, Transfection, Tumor Cells, Cultured, Cysteine Proteinase Inhibitors, Genes, Tumor Suppressor, Protein Isoforms, Tumor Suppressor Proteins, Papillomaviridae, Proteasome Endopeptidase Complex, Proto-Oncogene Proteins c-mdm2
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