ArticleOncogene2012
Functional analysis and consequences of Mdm2 E3 ligase inhibition in human tumor cells.
Article in Oncogene, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- RING finger E3 ubiquitin ligases: novel therapeutic opportunities in melanoma.Cellular & molecular biology letters · 2026Review
- Review
- Prognostic implications of MDM2 expression in surgically resected epidermal growth factor receptor mutant lung cancer with pathological lymph node metastasis.Translational lung cancer research · 2025Article
- MDM2- an indispensable player in tumorigenesis.Molecular biology reports · 2023Review
- MDM2, MDMX, and p73 regulate cell-cycle progression in the absence of wild-type p53.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Melatonin: Regulation of Biomolecular Condensates in Neurodegenerative Disorders.Antioxidants (Basel, Switzerland) · 2021Review
- Ubiquitin-Specific Proteases: Players in Cancer Cellular Processes.Pharmaceuticals (Basel, Switzerland) · 2021Review
- LG-ESSs and HG-ESSs: underlying molecular alterations and potential therapeutic strategies.Journal of Zhejiang University. Science. B · 2021Review
- Anti-proliferative, pro-apoptotic and anti-invasive effect of the copper coordination compound Cas III-La through the induction of reactive oxygen species and regulation of Wnt/β-catenin pathway in glioma.Journal of Cancer · 2021Article
- The emerging role for Cullin 4 family of E3 ligases in tumorigenesis.Biochimica et biophysica acta. Reviews on cancer · 2019Review
- Development of a novel immunoassay to detect interactions with the transactivation domain of p53: application to screening of new drugs.Scientific reports · 2017Article
- Essential Roles of E3 Ubiquitin Ligases in p53 Regulation.International journal of molecular sciences · 2017Review
- MDM2 oligomers: antagonizers of the guardian of the genome.Oncogene · 2016Review
- Regulation of the DNA damage response by ubiquitin conjugation.Frontiers in genetics · 2015Review
- Mir-509-5p joins the Mdm2/p53 feedback loop and regulates cancer cell growth.Cell death & disease · 2014Article
- In vivo activation of the p53 tumor suppressor pathway by an engineered cyclotide.Journal of the American Chemical Society · 2013Article
- p53 Regulation Goes Live-Mdm2 and MdmX Co-Star: Lessons Learned from Mouse Modeling.Genes & cancer · 2012Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 3 countries.
Funding
Abstract
Mdm2 is the major negative regulator of p53 tumor-suppressor activity. This oncoprotein is overexpressed in many human tumors that retain the wild-type p53 allele. As such, targeted inhibition of Mdm2 is being considered as a therapeutic anticancer strategy. The N-terminal hydrophobic pocket of Mdm2 binds to p53 and thereby inhibits the transcription of p53 target genes. Additionally, the C-terminus of Mdm2 contains a RING domain with intrinsic ubiquitin E3 ligase activity. By recruiting E2 ubiquitin-conjugating enzyme(s), Mdm2 acts as a molecular scaffold to facilitate p53 ubiquitination and proteasome-dependent degradation. Mdmx (Mdm4), an Mdm2 homolog, also has a RING domain and hetero-oligomerizes with Mdm2 to stimulate its E3 ligase activity. Recent studies have shown that C-terminal residues adjacent to the RING domain of both Mdm2 and Mdmx contribute to Mdm2 E3 ligase activity. However, the molecular mechanisms mediating this process remain unclear, and the biological consequences of inhibiting Mdm2/Mdmx co-operation or blocking Mdm2 ligase function are relatively unexplored. This study presents biochemical and cell biological data that further elucidate the mechanisms by which Mdm2 and Mdmx co-operate to regulate p53 level and activity. We use chemical and genetic approaches to demonstrate that functional inhibition of Mdm2 ubiquitin ligase activity is insufficient for p53 activation. This unexpected result suggests that concomitant treatment with Mdm2/Mdmx antagonists may be needed to achieve therapeutic benefit.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.