Cited by 653Cancer-related Molecular PathwaysUbiquitin and proteasome pathwaysHeat shock proteins research

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MDM2 — master regulator of the p53 tumor suppressor protein

Momand, Jamil, Wu, Hsiao-Huei, Dasgupta, Gargi·2000·Gene

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Abstract

MDM2 is an oncogene that mainly functions to modulate p53 tumor suppressor activity. In normal cells the MDM2 protein binds to the p53 protein and maintains p53 at low levels by increasing its susceptibility to proteolysis by the 26S proteosome. Immediately after the application of cellular stress, the ability of MDM2 to bind to p53 is blocked or altered in a fashion that prevents MDM2-mediated degradation. As a result, p53 levels rise, causing cell cycle arrest or apoptosis. In this review, we present evidence for the existence of three highly conserved regions (CRs) shared by MDM2 proteins and MDMX proteins of different species. These highly conserved regions encompass residues 42-94 (CR1), 301-329 (CR2), and 444-483 (CR3) on human MDM2. These three domains are respectively important for binding p53, for binding the retinoblastoma protein, and for transferring ubiquitin to p53. This review discusses the major milestones uncovered in MDM2 research during the past 12 years and potential uses of this knowledge in the fight against cancer.

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See all 653

Authors: Momand, J., Wu, H.-H., & Dasgupta, G.
Affiliations: California State University Los Angeles (US)
Corresponding author: Momand, Jamil
ORCID: Momand, Jamil
Wu, Hsiao-Huei
Venue: Gene
Publisher: Elsevier BV
Published: 2000-01
Volume: 242
Issue: 1-2
Pages: 15-29
ISSN: 0378-1119 (ISSN-L)
DOI: 10.1016/s0378-1119(99)00487-4
OpenAlex: W1973821009
Cited by: 641
References: 144
Citations by year: 2026: 6 · 2025: 11 · 2024: 17 · 2023: 19 · 2022: 24 · 2021: 10 · 2020: 17 · 2019: 16 · 2018: 22 · 2017: 14 · 2016: 17 · 2015: 31 · 2014: 21 · 2013: 21 · 2012: 24
FWCI: 4.03
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Gene (publishedVersion)
PubMed (publishedVersion)
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, p53, tumor suppressor regulation, MDMX, conserved domains, p53 ubiquitination, proteasomal degradation, cell cycle arrest, apoptosis, oncogenes, cancer therapy
MeSH terms: Amino Acid Sequence, Animals, Gene Expression Regulation, Humans, Models, Biological, Molecular Sequence Data, Nuclear Proteins, Proto-Oncogene Proteins, Genes, Tumor Suppressor, Tumor Suppressor Protein p53, Sequence Homology, Amino Acid, Proto-Oncogene Proteins c-mdm2

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MDM2 — master regulator of the p53 tumor suppressor protein

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