A subset of tumor-derived mutant forms of p53 down-regulate p63 and p73 through a direct interaction with the p53 core domain

Gaiddon, C.; Lokshin, M.; Ahn, J.; Zhang, T.; Prives, C.

doi:10.1128/mcb.21.5.1874-1887.2001

Cited by 464Cancer-related Molecular PathwaysHeat shock proteins researchCell death mechanisms and regulation

A subset of tumor-derived mutant forms of p53 down-regulate p63 and p73 through a direct interaction with the p53 core domain

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Gaiddon, C., Lokshin, M., Ahn, J., Zhang, T., Prives, C.·2001·Molecular and Cellular Biology

DOI 10.1128/mcb.21.5.1874-1887.2001PMC PMC86759

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Abstract

The p53 protein is related by sequence homology and function to the products of two other genes, p63 and p73, that each encode several isoforms. We and others have discovered previously that certain tumor-derived mutants of p53 can associate and inhibit transcriptional activation by the alpha and beta isoforms of p73. In this study we have extended these observations to show that in transfected cells a number of mutant p53 proteins could bind and down-regulate several isoforms not only of p73 (p73 alpha, -beta, -gamma, and -delta) but also of p63 (p63 alpha and -gamma; Delta Np63 alpha and -gamma). Moreover, a correlation existed between the efficiency of p53 binding and the inhibition of p63 or p73 function. We also found that wild-type p63 and p73 interact efficiently with each other when coexpressed in mammalian cells. The interaction between p53 mutants and p63 or p73 was confirmed in a physiological setting by examining tumor cell lines that endogenously express these proteins. We also demonstrated that purified p53 and p73 proteins interact directly and that the p53 core domain, but not the tetramerization domain, mediates this interaction. Using a monoclonal antibody (PAb240) that recognizes an epitope within the core domain of a subset of p53 mutants, we found a correlation between the ability of p53 proteins to be immunoprecipitated by this antibody and their ability to interact with p73 or p63 in vitro and in transfected cells. Based on these results and those of others, we propose that interactions between the members of the p53 family are likely to be widespread and may account in some cases for the ability of tumor-derived p53 mutants to promote tumorigenesis.

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“Moreover, mut-p53 inhibition of p63 and p73 promotes tumor cell invasion [80,81].”
From The p53 Pathway in Glioblastoma (2018) · cites this paper as [80]

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Authors: Gaiddon, C., Lokshin, M., Ahn, J., Zhang, T., & Prives, C.
Affiliations: Columbia University (US)
Corresponding author: Prives, C.
ORCID: Gaiddon, C.
Prives, C.
Venue: Molecular and Cellular Biology
Publisher: Informa UK Limited
Published: 2001-03-01
Volume: 21
Issue: 5
Pages: 1874-1887
ISSN: 0270-7306 (ISSN-L)
1098-5549
DOI: 10.1128/mcb.21.5.1874-1887.2001
PMC: PMC86759
OpenAlex: W2130521757
Cited by: 464
References: 72
Citations by year: 2026: 1 · 2025: 6 · 2024: 14 · 2023: 16 · 2022: 17 · 2021: 15 · 2020: 18 · 2019: 15 · 2018: 18 · 2017: 17 · 2016: 26 · 2015: 17 · 2014: 33 · 2013: 15 · 2012: 35
FWCI: 10.44
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Molecular and Cellular Biology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion)
Funders: National Institutes of Health
National Cancer Institute (R01CA077742, CA77742)
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, p63, p73, mutant p53, p53 core domain, protein-protein interaction, p73 isoforms, p63 isoforms, ΔNp63, carcinogenesis, p53 family
MeSH terms: Tumor Protein p73, Antibodies, Monoclonal, Cells, Cultured, DNA-Binding Proteins, Genetic Vectors, Humans, Luciferases, Membrane Proteins, Mutation, Neoplasms, Nuclear Proteins, Phosphoproteins, Precipitin Tests, Protein Binding, Transcription Factors, Transfection, Tumor Cells, Cultured, Transcriptional Activation, Trans-Activators, Down-Regulation, Genes, Tumor Suppressor, Genes, p53, Tumor Suppressor Protein p53, Protein Structure, Tertiary, Genes, Reporter, HSP70 Heat-Shock Proteins, Protein Isoforms, Tumor Suppressor Proteins, HSC70 Heat-Shock Proteins

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A subset of tumor-derived mutant forms of p53 down-regulate p63 and p73 through a direct interaction with the p53 core domain

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