Cited by 334Cancer-related Molecular PathwaysHeat shock proteins researchCell death mechanisms and regulation

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MDM2 Suppresses p73 Function without Promoting p73 Degradation

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Zeng, Xiaoya, Chen, Lihong, Jost, Christine A., Maya, Ruth, Keller, David, Wang, Xinjiang, Kaelin, William G., Oren, Moshe, Chen, Jiandong, Lu, Hua·1999·Molecular and Cellular Biology

DOI 10.1128/mcb.19.5.3257PMC PMC84120

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Abstract

The newly identified p53 homolog p73 can mimic the transcriptional activation function of p53. We investigated whether p73, like p53, participates in an autoregulatory feedback loop with MDM2. p73 bound to MDM2 both in vivo and in vitro. Wild-type but not mutant MDM2, expressed in human p53 null osteosarcoma Saos-2 cells, inhibited p73- and p53-dependent transcription driven by the MDM2 promoter-derived p53RE motif as measured in transient-transfection and chloramphenicol acetyltransferase assays and also inhibited p73-induced apoptosis in p53-null human lung adenocarcinoma H1299 cells. MDM2 did not promote the degradation of p73 but instead disrupted the interaction of p73, but not of p53, with p300/CBP by competing with p73 for binding to the p300/CBP N terminus. Both p73alpha and p73beta stimulated the expression of the endogenous MDM2 protein. Hence, MDM2 is transcriptionally activated by p73 and, in turn, negatively regulates the function of this activator through a mechanism distinct from that used for p53 inactivation.

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BackgroundResultInfluential
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Retracted
Deferasirox-Dependent Iron Chelation Enhances Mitochondrial Dysfunction and Restores p53 Signaling by Stabilization of p53 Family Members in Leukemic Cells
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Authors: Zeng, X., Chen, L., Jost, C. A., Maya, R., Keller, D., Wang, X., Kaelin, W. G., Oren, M., Chen, J., & Lu, H.
Affiliations: Oregon Health & Science University (US)
Louisiana State University (US)
Harvard University (US)
Weizmann Institute of Science (IL)
Howard Hughes Medical Institute (US)
ORCID: Chen, Lihong
Maya, Ruth
Wang, Xinjiang
Kaelin, William G.
Oren, Moshe
Chen, Jiandong
Lu, Hua
Venue: Molecular and Cellular Biology
Publisher: Informa UK Limited
Published: 1999-05
Volume: 19
Issue: 5
Pages: 3257-3266
ISSN: 0270-7306 (ISSN-L)
1098-5549
DOI: 10.1128/mcb.19.5.3257
PMC: PMC84120
OpenAlex: W2106031335
Cited by: 334
References: 65
Citations by year: 2026: 3 · 2025: 1 · 2024: 1 · 2023: 6 · 2022: 6 · 2021: 6 · 2020: 9 · 2019: 8 · 2018: 7 · 2017: 6 · 2016: 5 · 2015: 13 · 2014: 10 · 2013: 11 · 2012: 12
FWCI: 13.51
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)
Funders: National Cancer Institute (R01 CA 79721-01, R01CA079721)
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: MDM2, p73, p53, CBP/p300, transcriptional activation, autoregulatory loop, p53 response elements, apoptosis, protein-protein interaction, p73alpha, p53-null cells
MeSH terms: Tumor Protein p73, DNA-Binding Proteins, Feedback, Fluorescent Antibody Technique, Gene Expression Regulation, Humans, Mutation, Nuclear Proteins, Protein Binding, Proto-Oncogene Proteins, Recombinant Proteins, Transcription, Genetic, Tumor Cells, Cultured, Transcriptional Activation, Trans-Activators, Genes, Tumor Suppressor, Tumor Suppressor Protein p53, Apoptosis, Genes, Reporter, Tumor Suppressor Proteins, Proto-Oncogene Proteins c-mdm2

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MDM2 Suppresses p73 Function without Promoting p73 Degradation

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