MDM2 and MDMX can interact differently with ARF and members of the p53 family
Abstract
Members of the p53 family of transcription factors have essential roles in tumor suppression and in development. MDM2 is an essential regulator of p53 that can inhibit the transcriptional activity of p53, shuttle p53 out of the nucleus, and target p53 for ubiquitination-mediated degradation. Little is known about the interaction and selectivity of different members of the p53 family (p53, p63, and p73) and the MDM2 family (MDM2 and MDMX). Here we show that the transcriptional activities of p53 and p73, but not that of p63, were inhibited by both MDM2 and MDMX. Consistent with these, we found that MDMX can physically interact with p53 and p73, but not with p63. Moreover, ectopically expressed MDM2 and MDMX could induce alterations in the subcellular localization of p73, but did not affect the subcellular localization of p53 and p63. Finally, we demonstrate that while ARF can interact with MDM2 and inhibit the regulation of p53 by MDM2, no interaction was found between ARF and MDMX. These data reveal that significant differences and selectivity exist between the regulation of different members of the p53 family by MDM2 and MDMX.
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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 [83]
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- Authors
- Wang, X., Arooz, T., Siu, W. Y., Chiu, C. H. S., Lau, A., Yamashita, K., & Poon, R. Y. C.
- Affiliations
- Hong Kong University of Science and Technology (HK)
- Kanazawa University (JP)
- Corresponding author
- Poon, Randy Y.C
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 2001-02-16
- Volume
- 490
- Issue
- 3
- Pages
- 202-208
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W2053003378
- Cited by
- 94
- References
- 56
- Citations by year
- 2023: 4 · 2022: 1 · 2021: 1 · 2020: 4 · 2019: 1 · 2018: 4 · 2017: 3 · 2016: 6 · 2014: 5 · 2012: 6
- FWCI
- 2.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Funders
- Israel Cancer Research Fund
- Princeton University
- 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, MDMX, p53 family, p53, p63, p73, ARF, protein-protein interaction, transcriptional regulation, subcellular localization, tumor suppression, ubiquitination, p53 degradation
- MeSH terms
- Tumor Protein p73, DNA-Binding Proteins, Fluorescent Antibody Technique, Gene Expression Regulation, Humans, Membrane Proteins, Nuclear Proteins, Phosphoproteins, Protein Binding, Proto-Oncogene Proteins, Recombinant Fusion Proteins, Substrate Specificity, Transcription Factors, Transcription, Genetic, Transfection, Tumor Cells, Cultured, Trans-Activators, Genes, Tumor Suppressor, Tumor Suppressor Protein p53, ADP-Ribosylation Factors, Protein Transport, Tumor Suppressor Proteins, Proto-Oncogene Proteins c-mdm2
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