ArticleThe EMBO journal2006
p53 mediates the negative regulation of MDM2 by orphan receptor TR3.
Article in The EMBO journal, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 69 citations in OpenAlex.
- Disruption of macrophage migration inhibitory factor signaling induces major tumor-associated macrophage phenotypes in human M2 macrophages.Molecular biomedicine · 2026Article
- NR4A1 expression aberrations contribute to radiotherapy resistance in gastric cancer.Scientific reports · 2025Article
- p53-miR-34a feedback in lung fibroblasts regulates antifibrotic effects of CSP7, nintedanib, and pirfenidone.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Functional Changes Associated With the Subcellular Localization of the Nuclear Receptor NR4A1.Biochemistry research international · 2025Review
- Radiosensitization effect of quinoline-indole-schiff base derivative 10E on non-small cell lung cancer cells in vitro and in tumor xenografts.Investigational new drugs · 2024Article
- Oxidative stress impairs the Nur77-Sirt1 axis resulting in a decline in organism homeostasis during aging.Aging cell · 2023Article
- Therapeutic potential of NR4A1 in cancer: Focus on metabolism.Frontiers in oncology · 2022Review
- Hypoxia-induced Nur77 activates PI3K/Akt signalingTheranostics · 2021Article
- Nuclear receptor 4A2 (NR4A2) is a druggable target for glioblastomas.Journal of neuro-oncology · 2020Article
- MT1G serves as a tumor suppressor in hepatocellular carcinoma by interacting with p53.Oncogenesis · 2019Article
- Dual targeting of Nur77 and AMPKα by isoalantolactone inhibits adipogenesis in vitro and decreases body fat mass in vivo.International journal of obesity (2005) · 2019Article
- Article
- Characteristics of Nur77 and its ligands as potential anticancer compounds (Review).Molecular medicine reports · 2018Review
- NR4A1 retards adipocyte differentiation or maturation via enhancing GATA2 and p53 expression.Journal of cellular and molecular medicine · 2018Article
- New Drug Candidate Targeting the 4A1 Orphan Nuclear Receptor for Medullary Thyroid Cancer Therapy.Molecules (Basel, Switzerland) · 2018Article
- Transforming Growth Factor β/NR4A1-Inducible Breast Cancer Cell Migration and Epithelial-to-Mesenchymal Transition Is p38α (Mitogen-Activated Protein Kinase 14) Dependent.Molecular and cellular biology · 2017Article
- p53 and miR-34a Feedback Promotes Lung Epithelial Injury and Pulmonary Fibrosis.The American journal of pathology · 2017Article
- Nur77 suppresses hepatocellular carcinoma via switching glucose metabolism toward gluconeogenesis through attenuating phosphoenolpyruvate carboxykinase sumoylation.Nature communications · 2017Article
- Nur77 attenuates endothelin-1 expression via downregulation of NF-κB and p38 MAPK in A549 cells and in an ARDS rat model.American journal of physiology. Lung cellular and molecular physiology · 2016Article
- Transcriptomic Analysis Implicates the p53 Signaling Pathway in the Establishment of HIV-1 Latency in Central Memory CD4 T Cells in an In Vitro Model.PLoS pathogens · 2016Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
MDM2 is an oncoprotein whose transforming potential is activated by overexpression. The expression level of MDM2 is negatively regulated by orphan receptor TR3 that mainly acts as a transcriptional factor to regulate gene expression. However, the underlying mechanism is largely unclear. Here, we present the first evidence that inhibition of TR3 on MDM2 is mediated by p53. We found that TR3 directly interacts with p53 but not MDM2, and such interaction is critical for TR3 to inhibit MDM2 expression. TR3 downregulates p53 transcriptional activity by blocking its acetylation, leading to a decrease on the transcription level of MDM2. Furthermore, TR3 binding to p53 obstructs its ubiquitination and degradation induced by MDM2, resulting in the MDM2 ubiquitination and degradation. In addition, TR3 could enhance p53-mediated apoptosis induced by UV irradiation. Taken together, our findings demonstrate that p53 mediates the suppression of TR3 on MDM2 at both transcriptional and post-transcriptional level and suggest TR3 as a potential target to develop new anticancer agents that restrict MDM2-induced tumor progression.
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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.