ArticleCell death & disease2024
MDM4 inhibits ferroptosis in p53 mutant colon cancer via regulating TRIM21/GPX4 expression.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- TRAPPC4 Promotes GPX4 Stability to Drive Ferroptosis Resistance and Tumor Progression in Head and Neck Squamous Cell Carcinoma.Cancer research · 2026Article
- Pin1 targets phosphorylated NCOA4 for K29/K48-linked ubiquitination to suppress ferritinophagy and ferroptosis in anaplastic thyroid cancer.Cell death & disease · 2026Article
- Dual regulation of metabolic reprogramming and protein competitive modifications: the core role and mechanism of MRPL36 in glioblastoma malignant progression.Journal of experimental & clinical cancer research : CR · 2026Article
- Rv1983 promotes mycobacterial dissemination by triggering ferroptosis through GPX4 ubiquitination.Cellular & molecular biology letters · 2026Article
- Genetic mutations governing ferroptosis sensitivity and resistance: a precision approach to cancer therapy.Cell death & disease · 2026Review
- MDM4 at the Crossroads: Beyond p53 and MDM2.Cancers · 2026Review
- SFTA2 reduced colorectal cancer ferroptosis promoting metastasis through regulating EMT transition by degradation of Nrf2.Food & nutrition research · 2026Article
- Post-Translational Modifications: Key "Regulators" of Pancreatic Cancer Malignant Phenotype-Advances in Mechanisms and Targeted Therapies.Biomedicines · 2025Review
- MDMX reprograms glycolysis of hepatocellular carcinoma via 14-3-3γ/FOXO1.Cell death discovery · 2025Article
- New evidence for the protective effect of gut microbiota regulation of ferroptosis-related proteins against osteoporosis.World journal of microbiology & biotechnology · 2025Article
- Article
- Dependence on Mdm2 for Mdm4 inhibition of p53 activity.Cancer letters · 2025Article
- Increased ZNF83 is a potential prognostic biomarker and regulates oxidative stress-induced ferroptosis in clear cell renal cell carcinoma.Journal of molecular medicine (Berlin, Germany) · 2025Article
- TRIM21-mediated METTL3 degradation promotes PDAC ferroptosis and enhances the efficacy of Anti-PD-1 immunotherapy.Cell death & disease · 2025Article
- Ferroptosis's Master Switch GPX4 emerges as universal biomarker for precision immunotherapy: a pan-cancer study withFrontiers in oncology · 2025Article
- A Super-Enhancer-Related Ferroptosis Signature Predicts Survival and Immune Microenvironment in Colon Cancer Based on Bioinformatics Analyses and Experimental Validation.IET systems biologyArticle
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Authors and funding
11 authors.
Funding
Abstract
MDM4 is one of the major regulators of p53. The biological effect of MDM4 on tumor is controversial, its role and molecular mechanism in colon cancer progression and prognosis are still unclear. In this study, we identify that MDM4 is significantly overexpressed in human colon cancer and high MDM4 expression was associated with poor prognosis of colon cancer with mutant p53. MDM4 inhibits the ubiquitination of the ferroptosis marker protein GPX4 at K167 and K191 by upregulating the protein expression level of the E3 ubiquitin ligase TRIM21, which promotes the polyubiquitination of GPX4 transfer from K48- to K63- linked ubiquitination. Thereby, MDM4 enhances the stability of GPX4 protein, inhibiting ferroptosis, increasing the resistance of colon cancer patients to chemotherapy, and promoting colon cancer progression. These findings elucidate the ferroptosis inhibition effect of MDM4 via regulating TRIM21/GPX4 on p53-mutated colon cancer and provide a potential therapeutic strategy for colon cancer therapy.
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