ArticleMolecular and cellular biology2019
Mutant p53 Sequestration of the MDM2 Acidic Domain Inhibits E3 Ligase Activity.
Article in Molecular and cellular biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- TAF1 aggravates ferroptosis by promoting the ubiquitin-mediated degradation of nuclear GPX4.Journal of Zhejiang University. Science. B · 2026Article
- ARTS and small-molecule ARTS mimetics upregulate p53 levels by promoting the degradation of XIAP.Apoptosis : an international journal on programmed cell death · 2024Article
- Acetylation halts missense mutant p53 aggregation and rescues tumor suppression in non-small cell lung cancers.iScience · 2023Article
- TP53 mutations in Romanian patients with colorectal cancer.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2023Article
- Targeting mutant p53 stabilization for cancer therapy.Frontiers in pharmacology · 2023Review
- Targeting Post-Translational Regulation of p53 in Colorectal Cancer by Exploiting Vulnerabilities in the p53-MDM2 Axis.Cancers · 2022Review
- It's Getting Complicated-A Fresh Look at p53-MDM2-ARF Triangle in Tumorigenesis and Cancer Therapy.Frontiers in cell and developmental biology · 2022Review
- Review
- Dysregulation of the Ubiquitin Proteasome System in Human Malignancies: A Window for Therapeutic Intervention.Cancers · 2021Review
- Regulating tumor suppressor genes: post-translational modifications.Signal transduction and targeted therapy · 2020Review
- Silencing CCNG1 protects MPC-5 cells from high glucose-induced proliferation-inhibition and apoptosis-promotion via MDM2/p53 signaling pathway.International urology and nephrology · 2020Article
- MDM2-C Functions as an E3 Ubiquitin Ligase.Cancer management and research · 2020Article
- Small cell carcinoma of the bladder: the characteristics of molecular alterations, treatment, and follow-up.Medical oncology (Northwood, London, England) · 2019Review
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Authors and funding
5 authors.
Funding
Abstract
Missense p53 mutants often accumulate in tumors and drive progression through gain of function. MDM2 efficiently degrades wild-type p53 but fails to degrade mutant p53 in tumor cells. Previous studies revealed that mutant p53 inhibits MDM2 autoubiquitination, suggesting that the interaction inhibits MDM2 E3 activity. Recent work showed that MDM2 E3 activity is stimulated by intramolecular interaction between the RING and acidic domains. Here, we show that in the mutant p53-MDM2 complex, the mutant p53 core domain binds to the MDM2 acidic domain with significantly higher avidity than wild-type p53. The mutant p53-MDM2 complex is deficient in catalyzing ubiquitin release from the activated E2 conjugating enzyme. An MDM2 construct with extra copies of the acidic domain is resistant to inhibition by mutant p53 and efficiently promotes mutant p53 ubiquitination and degradation. The results suggest that mutant p53 interferes with the intramolecular autoactivation mechanism of MDM2, contributing to reduced ubiquitination and increased accumulation in tumor cells.
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