Cited by 1,280Cancer-related Molecular PathwaysDevelopmental Biology and Gene RegulationCell death mechanisms and regulation

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Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53

Jones, Stephen N., Roe, Amy E., Donehower, Lawrence A., Bradley, Allan·1995·Nature

DOI 10.1038/378206a0

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Abstract

The Mdm2 proto-oncogene was originally identified as one of several genes contained on a mouse double minute chromosome present in a transformed derivative of 3T3 cells. Overexpression of Mdm2 can immortalize primary cultures of rodent fibroblasts. Human MDM2 is amplified in 30-40% of sarcomas, and is overexpressed in leukaemic cells. The Mdm2 oncoprotein forms a complex with the p53 tumour-suppressor protein and inhibits p53-mediated transregulation of gene expression. Because Mdm2 expression increases in response to p53, Mdm2-p53 binding may autoregulate Mdm2 expression and modulate the activity of p53 in the cell. We have created Mdm2-null and Mdm2/p53-null mice to determine whether Mdm2 possesses developmental functions in addition to the ability to complex with p53, and to investigate the biological role of Mdm2-p53 complex formation in development. Mice deficient for Mdm2 die early in development. In contrast, mice deficient for both Mdm2 and p53 develop normally and are viable. These results suggest that a critical role of Mdm2 in development is the regulation of p53 function.

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Authors: Jones, S. N., Roe, A. E., Donehower, L. A., & Bradley, A.
Affiliations: Howard Hughes Medical Institute (US)
Baylor College of Medicine (US)
ORCID: Bradley, Allan
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 1995-11
Volume: 378
Issue: 6553
Pages: 206-208
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/378206a0
OpenAlex: W1993864973
Semantic Scholar: efc84bf5f5d1747443a3eb4555f9b5ede31b368f
Cited by: 1,280
References: 24
Citations by year: 2026: 9 · 2025: 17 · 2024: 30 · 2023: 31 · 2022: 28 · 2021: 35 · 2020: 41 · 2019: 28 · 2018: 31 · 2017: 38 · 2016: 54 · 2015: 34 · 2014: 59 · 2013: 30 · 2012: 60
FWCI: 14.50
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords: MDM2, p53, embryonic lethality, developmental regulation, tumor suppressor, sarcoma, leukemia
MeSH terms: Proto-Oncogene Mas, Animals, Base Sequence, Cell Cycle, Cell Line, Crosses, Genetic, Female, Embryonic and Fetal Development, Genes, Lethal, Molecular Sequence Data, Mutation, Nuclear Proteins, Proto-Oncogene Proteins, Tumor Suppressor Protein p53, 3T3 Cells, DNA Primers, Gene Targeting, Mice, Proto-Oncogene Proteins c-mdm2

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Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53

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