ArticleNature cell biology2025
PRMT5-mediated arginine methylation stabilizes GPX4 to suppress ferroptosis in cancer.
Article in Nature cell biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
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Who cites it
40 citing papers in PubMed.
- Protein arginine methylation and ubiquitination: A prominent crosstalk and its functions in cancer.Genes & diseases · 2026Review
- CD112 Lactylation Drives Dual Immune Evasion From CD8+ T Cells and NK Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- PRMT5 promotes ferroptosis in cisplatin-induced acute kidney injury through WDR5/ACSL4 pathway.Redox biology · 2026Article
- Article
- Mitochondrial hub: the integrative axis connecting ferroptosis and metabolic reprogramming in periodontitis.Molecular biology reports · 2026Review
- Role of PRMT5 in regulating ferritinophagy during Mycobacterium tuberculosis infection.PLoS pathogens · 2026Article
- Regulation of Glutathione Peroxidase 4 in Diabetic Retinopathy.International journal of molecular sciences · 2026Article
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- TRAPPC4 Promotes GPX4 Stability to Drive Ferroptosis Resistance and Tumor Progression in Head and Neck Squamous Cell Carcinoma.Cancer research · 2026Article
- Selenoproteins: Minute yet vital players governing cellular fate.Genes & diseases · 2026Review
- Article
- Translating ferroptosis into oncology: challenges, opportunities and future directions.Nature reviews. Clinical oncology · 2026Review
- Spermidine-functionalized Janus hydrogel microneedles inhibit ferroptosis and promote healing of oral ulcers.Bioactive materials · 2026Article
- Cell death pathways and targeting therapeutics in cancer therapy.Acta pharmacologica Sinica · 2026Review
- The role of STAT3 in regulating ferroptosis in cancer: molecular mechanisms and targeted therapeutic perspectives.Cancer gene therapy · 2026Review
- USP20 governs tyrosine kinase inhibitors resistance through ferroptosis evasion by targeting GPX4 in cancers.Redox biology · 2026Article
- TGM2-mediated serotonylation of GPX4 confers ferroptosis resistance to promote gastric tumorigenesis.Cell discovery · 2026Article
- Identification and diagnostic model construction of cuproptosis-related biomarkers in bone metastatic prostate cancer.Translational andrology and urology · 2026Article
- Protein arginine methyltransferases in cancer: mechanisms, functions, and therapeutic opportunities.Journal of biomedical science · 2026Review
- Methionine metabolism is linked with phospholipid and glutamine metabolism to drive ferroptosis.Cell reports · 2026Article
Corrections and comments
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Authors and funding
22 authors.
Funding
Abstract
The activation of ferroptosis has shown great potential for cancer therapy from an unconventional perspective, but revealing the mechanisms underlying the suppression of tumour-intrinsic ferroptosis to promote tumorigenesis remains a challenging task. Here we report that methionine is metabolized into S-adenosylmethionine, which functions as a methyl-group donor to trigger symmetric dimethylation of glutathione peroxidase 4 (GPX4) at the conserved arginine 152 (R152) residue, along with a prolonged GPX4 half-life. Inhibition of protein arginine methyltransferase 5 (PRMT5), which catalyses GPX4 methylation, decreases GPX4 protein levels by impeding GPX4 methylation and increasing ferroptosis inducer sensitivity in vitro and in vivo. This methylation prevents Cullin1-FBW7 E3 ligase binding to GPX4, thereby abrogating the ubiquitination-mediated GPX4 degradation. Notably, combining PRMT5 inhibitor treatment with ferroptotic therapies markedly suppresses tumour progression in mouse tumour models. In addition, the levels of GPX4 are negatively correlated with the levels of FBW7 and a poor prognosis in patients with human carcinoma. In summary, we found that PRMT5 functions as a target for improving cancer therapy efficacy, by acting to reduce the counteraction of ferroptosis by tumour cells by means of PRMT5-enhanced GPX4 stability.
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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.