ArticlePLoS genetics2022
MDM2 E3 ligase activity is essential for p53 regulation and cell cycle integrity.
Article in PLoS genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 31 citations in OpenAlex.
- Article
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- The RING E3 ligase RLIM drives oxidative stress-induced stem cell dysfunction through MDM2-p53 signaling.The Journal of biological chemistry · 2026Article
- Endocytic Control of Cell-Autonomous and Non-Cell-Autonomous Functions of p53.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Incorporation of network pharmacology, molecular docking, survival, density functional theory, and experimental studies to explore the potential key targets of formononetin by TERT-mediated anti-cancer effects in MCF-7 breast cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- MDM4 at the Crossroads: Beyond p53 and MDM2.Cancers · 2026Review
- Discontinued BACE1 Inhibitors in Phase II/III Clinical Trials and AM-6494 (Preclinical) Towards Alzheimer's Disease Therapy: Repurposing Through Network Pharmacology and Molecular Docking Approach.Pharmaceuticals (Basel, Switzerland) · 2026Article
- The guardian of the genome meets immunotherapy: p53-based strategies.Frontiers in immunology · 2026Review
- Molecular Characteristics, Circularization Mechanism, and Potential Functions of circRNA-0172.Genes · 2025Article
- The E3 ligase MEX3B forms a tripartite complex withOpen biology · 2025Article
- Exploration of the mechanism of curcumin in the regulation of apoptosis for the treatment of colorectal cancer.Translational cancer research · 2025Article
- In Silico Analysis Reveals MDM2 as a Potential Target of Ursolic Acid for Overcoming Tamoxifen Resistance in Breast Cancer.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- Anticancer Quinolinol Small Molecules Target Multiple Pathways to Promote Cell Death and Eliminate Melanoma Cells Resistant to BRAF Inhibitors.Molecules (Basel, Switzerland) · 2025Article
- Marine natural product Methyl mycophenolate inhibits gastric cancer growth through regulating p53 and the downstream pathways.Cancer cell international · 2025Article
- Inorganic Arsenic Induces Elevated p53 Levels with Altered Functionality Impacting the Expression of Toll-like Receptor 3 and Other Target Genes in Immortalized Prostate Epithelial Cells.International journal of molecular sciences · 2025Article
- Molecular analysis of HPV16 and HPV18 oncogenes in oral squamous cell carcinoma: Structural, transcriptomic andOncology letters · 2025Article
- A Perspective on Therapeutic Targeting Against Ubiquitin Ligases to Stabilize Tumor Suppressor Proteins.Cancers · 2025Review
- Novel Inhibitors for MDM2-MDM4 E3 Ligase Potently Induce p53-Indepedent Apoptosis in Drug-Resistant Leukemic Cells.Molecules (Basel, Switzerland) · 2025Article
- Role of Ubiquitin-regulated EMT in Cancer Metastasis and Chemoresistance.International journal of biological sciences · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
MDM2 and MDM4 are key regulators of p53 and function as oncogenes when aberrantly expressed. MDM2 and MDM4 partner to suppress p53 transcriptional transactivation and polyubiquitinate p53 for degradation. The importance of MDM2 E3-ligase-mediated p53 regulation remains controversial. To resolve this, we generated mice with an Mdm2 L466A mutation that specifically compromises E2 interaction, abolishing MDM2 E3 ligase activity while preserving its ability to bind MDM4 and suppress p53 transactivation. Mdm2L466A/L466A mice exhibit p53-dependent embryonic lethality, demonstrating MDM2 E3 ligase activity is essential for p53 regulation in vivo. Unexpectedly, cells expressing Mdm2L466A manifest cell cycle G2-M transition defects and increased aneuploidy even in the absence of p53, suggesting MDM2 E3 ligase plays a p53-independent role in cell cycle regulation and genome integrity. Furthermore, cells bearing the E3-dead MDM2 mutant show aberrant cell cycle regulation in response to DNA damage. This study uncovers an uncharacterized role for MDM2's E3 ligase activity in cell cycle beyond its essential role in regulating p53's stability in vivo.
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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.