ArticleNature chemical biology2022
Ribosome stalling during selenoprotein translation exposes a ferroptosis vulnerability.
Article in Nature chemical biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed, 125 citations in OpenAlex.
- Targeted extracellular degradation of LRP8 promotes ferroptosis in cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Mechanisms underlying propagation of ferroptotic cell death.Nature cell biology · 2026Review
- Emerging tools to investigate the contribution of selenium to ferroptosis and beyond.Nature chemical biology · 2026Review
- Targeting oncogenic FLT3 uncovers a ferroptosis vulnerability through selenocysteine recoding in acute myeloid leukaemia.Nature cell biology · 2026Article
- Biomaterial-based strategies targeting ferroptosis for alleviating intervertebral disc degeneration: Advances and perspectives.Journal of orthopaedic translation · 2026Review
- Ferroptosis as an approach to leverage cancer metabolism.Trends in cell biology · 2026Review
- Poly-GR promotes ferroptosis-associated vulnerability in C9orf72-ALS.Cell & bioscience · 2026Article
- Genetics of selenoproteins and selenoprotein metabolism - An overview of current concepts and emerging aspects.Redox biology · 2026Review
- GPX4-dependent ferroptosis governs ILC2 homeostasis and colitis progression.Cellular & molecular immunology · 2026Article
- Dissecting Complex Interactions Between Ferroptosis and the Proteasome.bioRxiv : the preprint server for biology · 2026Article
- Disruption of HSPA8-GEMIN5 interaction suppresses colorectal cancer by impaired splicing-translation coupling-mediated proteostasis imbalance.Journal of experimental & clinical cancer research : CR · 2026Article
- Regulation of apoptosis, ferroptosis, and pyroptosis mediated by acetylation.Cell death discovery · 2026Review
- Ferroptosis as an Emerging Therapeutic Target in Allergic Diseases.Drug design, development and therapy · 2026Review
- Ironing out COPD: ferroptosis-driven immune dysregulation, metabolic rewiring, and precision therapeutic opportunities.Frontiers in immunology · 2026Review
- Metabolic adaptations in cancer progression.Physiological reviews · 2026Review
- CPT1A as a metabolic gatekeeper linking fatty acid oxidation, ferroptosis resistance, and breast cancer stemness.Frontiers in oncology · 2026Review
- Ferroptosis regulation in doxorubicin-induced cardiotoxicity: multi-mechanism interventions and translational strategies.Frontiers in pharmacology · 2026Review
- Targeting GPX4 and FSP1 to exploit ferroptotic vulnerability in Ewing sarcoma.Frontiers in oncology · 2026Article
- Fueling Death: The Metabolic Control of Ferroptosis.Advances in experimental medicine and biology · 2026Review
- Ferroptosis in hematological malignancies: molecular mechanisms and therapeutic potential.Cellular oncology (Dordrecht, Netherlands) · 2025Review
26 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
The selenoprotein glutathione peroxidase 4 (GPX4) prevents ferroptosis by converting lipid peroxides into nontoxic lipid alcohols. GPX4 has emerged as a promising therapeutic target for cancer treatment, but some cancer cells are resistant to ferroptosis triggered by GPX4 inhibition. Using a chemical-genetic screen, we identify LRP8 (also known as ApoER2) as a ferroptosis resistance factor that is upregulated in cancer. Loss of LRP8 decreases cellular selenium levels and the expression of a subset of selenoproteins. Counter to the canonical hierarchical selenoprotein regulatory program, GPX4 levels are strongly reduced due to impaired translation. Mechanistically, low selenium levels result in ribosome stalling at the inefficiently decoded GPX4 selenocysteine UGA codon, leading to ribosome collisions, early translation termination and proteasomal clearance of the N-terminal GPX4 fragment. These findings reveal rewiring of the selenoprotein hierarchy in cancer cells and identify ribosome stalling and collisions during GPX4 translation as ferroptosis vulnerabilities in cancer.
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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.