The DOI matches its Crossref record; 134 of the 144 references it cites were found in a registry or an index.
MDM2 — master regulator of the p53 tumor suppressor protein
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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“The flanking sequences of Ser 166 are also conserved in mouse (Ser 163 ), dog (Ser 166 ), and zebrafish (Ser 146 ) but not in Xenopus (13,14).”
From Stabilization of Mdm2 via Decreased Ubiquitination Is Mediated by Protein Kinase B/Akt-dependent Phosphorylation (2004) · cites this paper as [13]
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Metadata
- Authors
- Momand, J., Wu, H.-H., & Dasgupta, G.
- Affiliations
- California State University Los Angeles (US)
- Corresponding author
- Momand, Jamil
- Venue
- Gene
- Publisher
- Elsevier BV
- Published
- 2000-01
- Volume
- 242
- Issue
- 1-2
- Pages
- 15-29
- ISSN
- 0378-1119 (ISSN-L)
- 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
- 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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