ArticleCell death & disease2023
The E3 ligase TRIM26 suppresses ferroptosis through catalyzing K63-linked ubiquitination of GPX4 in glioma.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 76 citations in OpenAlex.
- Ubiquitylome analysis reveals the protective effect of α-lipoic acid via the ferroptosis pathway during recovery after hepatic oxidative stress in finishing pigs.Stress biology · 2026Article
- Lactate-associated H3K18la upregulates RNF166 to promote immune evasion in hepatocellular carcinoma by remodeling c-Jun ubiquitination.Apoptosis : an international journal on programmed cell death · 2026Article
- S100A9 modulates USP7-mediated stabilization of NCOA4 to promote ferroptosis in sepsis-associated acute lung injury.Redox biology · 2026Article
- TRIM26 triggers ferroptosis via ZEB1 degradation to suppress nasopharyngeal carcinoma progression.Journal of molecular histology · 2026Article
- TRAPPC4 Promotes GPX4 Stability to Drive Ferroptosis Resistance and Tumor Progression in Head and Neck Squamous Cell Carcinoma.Cancer research · 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
- USP20 governs tyrosine kinase inhibitors resistance through ferroptosis evasion by targeting GPX4 in cancers.Redox biology · 2026Article
- Ubiquitin-Specific Protease 45 Inhibits Lung Adenocarcinoma Ferroptosis by Regulating Ubiquitination and Stability of Glutathione Peroxidase 4.Cancer medicine · 2026Article
- TRIM26-mediated NKRF degradation drives Osimertinib resistance through SNRPD2-dependent stress granule formation in lung adenocarcinoma.Cell death & disease · 2026Article
- TAF1 aggravates ferroptosis by promoting the ubiquitin-mediated degradation of nuclear GPX4.Journal of Zhejiang University. Science. B · 2026Article
- Aberrant expression of TRIM26 suppresses ferroptosis through regulating GPX4 protein stability in colorectal cancer.Molecular biology reports · 2026Article
- Inhibition of SDE2 promotes autophagy-dependent ferroptosis in multiple myeloma.Redox biology · 2026Article
- Dysregulation of post-translational modifications in glioma: advances in pathological mechanisms and clinical targeting strategies.Journal of translational medicine · 2026Review
- TRIM56 Aggravates Cerebral Ischemia-Reperfusion Injury via Inhibiting KLF4-Activated Ferroptosis Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Inhibition of Setd7 protects against cardiomyocyte hypertrophy via inhibiting lipid oxidation.Acta pharmacologica Sinica · 2026Article
- Rottlerin triggers dual degradation of SLC7A11 and GPX4 to drive ferroptosis and chemosensitization in hepatocellular carcinoma.Cell death discovery · 2026Article
- Targeting Ferroptosis for Cerebral Neuroprotection in Ischemic Stroke: Pathophysiological Insights.International journal of general medicine · 2026Review
- TRIM62 promotes osteoarthritis progression by facilitating GPX4 ubiquitination and chondrocyte ferroptosis.American journal of translational research · 2026Article
- Targeted Delivery of Schisandrin A to Cardiac Endothelium Alleviates Myocardial Ischemia-Reperfusion Injury via Suppression of Ferroptosis.International journal of nanomedicine · 2026Article
- Targeting glutathione peroxidase 4 in ferroptosis: from immune regulation to pharmacological development and translational applications.Frontiers in pharmacology · 2026Review
4 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The selenium-containing enzyme GPX4 moonlights as a central regulator of ferroptosis, an iron-dependent, nonapoptotic form of regulated cell death caused by lipid peroxidation. Yet, little is known about the mechanisms underlying the regulation of its post-transcriptional modifications. Here, we identify the tripartite motif-containing protein TRIM26 as an E3 ubiquitin ligase of GPX4. TRIM26 directly interacts with GPX4 through its Ring domain and catalyzes the ubiquitination of GPX4 at K107 and K117, which promotes the switch in polyubiquitination of GPX4 from K48 to K63, thus enhancing GPX4 protein stability. Moreover, PLK1-mediated S127 phosphorylation of TRIM26 enhances the interaction between TRIM26 and GPX4. Inhibition of TRIM26 phosphorylation causes a reduction in GPX4 K63-linked polyubiquitination and diminishes GPX4 protein levels in tumor cells. Further investigation revealed that TRIM26 is overexpressed in glioma cells. TRIM26 silencing dramatically impedes ferroptosis resistance and tumorigenesis in glioma in vivo and in vitro. Clinically, TRIM26 expression shows a direct correlation with GPX4 and PLK1 levels in glioma samples and is associated with poor outcome in patients with glioma. Collectively, these findings define the role of GPX4 K63-linked polyubiquitination in ferroptosis and suggest a potential strategy for glioma treatment.
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