ArticleCell2023
An E3 ligase network engages GCN1 to promote the degradation of translation factors on stalled ribosomes.
Article in Cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 74 citations in OpenAlex.
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- Genetic dissection reveals distinct contributions of the eS31 N-terminal domain to translational accuracy in Saccharomyces cerevisiae.The FEBS journal · 2026Article
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- Principles of ribosome-associated protein quality control during the synthesis of CFTR.The EMBO journal · 2026Article
- Targeting eEF1A1 With Baicalein to Block eEF1A1/Prdx4 Interaction for Treating Sepsis-Mediated Lung Injury.Exploration (Beijing, China) · 2026Article
- Synthetic Diastereomers of the Fungal Cycloheptapeptide Paraisariamide A Retain Ternatin-Like Biological Activity.ACS medicinal chemistry letters · 2026Article
- Enhancing Proteasome Activity in T Cells Alleviates Exhaustion and Improves Antitumor Immunity.Cancer research · 2026Article
- Glutamine codon-driven translational readthrough reveals context-dependent stop codon decoding fidelity.bioRxiv : the preprint server for biology · 2026Article
- The atypical E3 ligase HOIL-1 safeguards the ribosome during cellular stress.Nature cell biology · 2026Article
- Systematic transcriptome analysis reveals the function of alternative promoters in hematopoietic lineages.Stem cell reports · 2026Article
- Ribosome-associated quality control and related mechanisms.Nature structural & molecular biology · 2026Review
- Integrated phenotypic screening and chemical proteomics identifies ETF1 ligands that modulate viral translation and replication.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Quality control and signaling pathways at stalled ribosomes.Experimental & molecular medicine · 2026Review
- Ribosome-associated quality control of aberrant protein production during amino acid limitation.bioRxiv : the preprint server for biology · 2026Article
- Single-cell perturbations decipher ribosomal stress-surveillance regulators in type 2 diabetes.Nature metabolism · 2026Article
- Can plitidepsin be used as an antiviral against RSV?mSphere · 2025Article
- WEE1 inhibitors trigger GCN2-mediated activation of the integrated stress response.Nature communications · 2025Article
- Serine tRNAs compete to regulate the mRNA translation of serine-sensitive codons.Science advances · 2025Article
- Transcriptional downregulation of rhodopsin is associated with desensitization of rods to light-induced damage in a murine model of retinitis pigmentosa.Human molecular genetics · 2025Article
- Integrated bioinformatics analysis identifies RPS27A and PPP2R1A as shared hub genes in heart failure and COVID-19.Journal of cardiothoracic surgery · 2025Article
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7 authors at 1 institution in 1 country.
Funding
Abstract
Ribosomes frequently stall during mRNA translation, resulting in the context-dependent activation of quality control pathways to maintain proteostasis. However, surveillance mechanisms that specifically respond to stalled ribosomes with an occluded A site have not been identified. We discovered that the elongation factor-1α (eEF1A) inhibitor, ternatin-4, triggers the ubiquitination and degradation of eEF1A on stalled ribosomes. Using a chemical genetic approach, we unveiled a signaling network comprising two E3 ligases, RNF14 and RNF25, which are required for eEF1A degradation. Quantitative proteomics revealed the RNF14 and RNF25-dependent ubiquitination of eEF1A and a discrete set of ribosomal proteins. The ribosome collision sensor GCN1 plays an essential role by engaging RNF14, which directly ubiquitinates eEF1A. The site-specific, RNF25-dependent ubiquitination of the ribosomal protein RPS27A/eS31 provides a second essential signaling input. Our findings illuminate a ubiquitin signaling network that monitors the ribosomal A site and promotes the degradation of stalled translation factors, including eEF1A and the termination factor eRF1.
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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.