Comparative study of the p53-mdm2 and p53-MDMX interfaces
Abstract
Mdm2 and MDMX are two structurally related p53-binding proteins which show the highest level of sequence similarity in the N-terminal p53-binding domains. Apart from its ability to inhibit p53 mediated transcription, a feature it shares with mdm2, very little is known about the physiological functions of MDMX. It is clearly distinct from mdm2 since its expression appears not to be regulated by p53 and it cannot compensate for lack of mdm2 in early development. We present data on the structural similarity between the p53 binding pockets of mdm2 and MDMX using p53- and phage-selected peptides. From the results we conclude that our recently devised innovative approach to reverse the mdm2-mediated inhibition of p53's transactivation function in vivo would probably target MDMX as well. Strategies for selectively targeting mdm2 and MDMX are suggested and a possible mechanism for regulating the p53-mdm2/MDMX interactions by protein phosphorylation is discussed.
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S15 and S20 phosphorylation do not prevent MDM2 binding in vitro.
“However, biochemical analysis using phosphorylated p53 peptide indicated that S15 and S20 phosphorylation do not prevent MDM2 binding in vitro (Bottger et al, 1999).”
From ATM activates p53 by regulating MDM2 oligomerization and E3 processivity (2009) · cites this paper as Bottger et al, 1999
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- Authors
- Böttger, V., Böttger, A., Garcia-Echeverria, C., Ramos, Y. F., van der Eb, A. J., Jochemsen, A. G., & Lane, D. P.
- Affiliations
- University of Dundee (GB)
- Novartis (Switzerland) (CH)
- Leiden University Medical Center (NL)
- Venue
- Oncogene
- Published
- 1999-01-07
- Volume
- 18
- Issue
- 1
- Pages
- 189-199
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2332575792
- Cited by
- 189
- References
- 35
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 3 · 2023: 5 · 2022: 3 · 2021: 3 · 2020: 5 · 2019: 4 · 2018: 1 · 2017: 1 · 2016: 9 · 2015: 3 · 2014: 7 · 2013: 5 · 2012: 10
- FWCI
- 4.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (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 › Cell death mechanisms and regulation
- Keywords
- p53, MDM2, MDMX, p53-binding domain, protein-protein interaction, protein phosphorylation, tumor suppressor regulation
- MeSH terms
- Amino Acid Sequence, Humans, Molecular Sequence Data, Nuclear Proteins, Peptides, Proto-Oncogene Proteins, Recombinant Fusion Proteins, Solubility, Gene Expression, Tumor Suppressor Protein p53, Proto-Oncogene Proteins c-mdm2
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