ArticleThe Journal of biological chemistry2011
Evidence that eukaryotic translation elongation factor 1A (eEF1A) binds the Gcn2 protein C terminus and inhibits Gcn2 activity.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 54 citations in OpenAlex.
- Yeast Gcn2 retains activity following humanization of its auto-phosphorylation region.FEBS open bio · 2026Article
- Saccharomyces cerevisiae as a model for mammalian diseases.FEMS yeast research · 2026Review
- Depurination of sarcin/ricin loop 25S rRNA is signaled through the small ribosomal subunit during translation.RNA (New York, N.Y.) · 2025Article
- Purification and Analysis of eIF2α Phosphorylation by Stress-Activated Protein Kinase Gcn2 from S. cerevisiae.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Functional Analysis of the Yeast Counterpart to the Human GCN2 p.Glu738_Asp739insArgArg Variant.microPublication biology · 2025Article
- Translation regulation in response to stress.The FEBS journal · 2024Review
- Exploiting Translation Machinery for Cancer Therapy: Translation Factors as Promising Targets.International journal of molecular sciences · 2024Review
- eEF1α2 is required for actin cytoskeleton homeostasis in the aging muscle.Disease models & mechanisms · 2024Article
- Evidence that Xrn1 is in complex with Gcn1, and is required for full levels of eIF2α phosphorylation.The Biochemical journal · 2024Article
- Multiple Roles of the Stress Sensor GCN2 in Immune Cells.International journal of molecular sciences · 2023Review
- Zinc-finger protein Zpr1 is a bespoke chaperone essential for eEF1A biogenesis.Molecular cell · 2023Article
- Ribosome changes reprogram translation for chemosurvival in G0 leukemic cells.Science advances · 2022Article
- The Origins, Evolution, and Future of Dietary Methionine Restriction.Annual review of nutrition · 2022Review
- Identification of a modulator of the actin cytoskeleton, mitochondria, nutrient metabolism and lifespan in yeast.Nature communications · 2022Article
- Codon usage and protein length-dependent feedback from translation elongation regulates translation initiation and elongation speed.Nucleic acids research · 2021Article
- Mutagenesis screen uncovers lifespan extension through integrated stress response inhibition without reduced mRNA translation.Nature communications · 2021Article
- Damaging de novo missense variants in EEF1A2 lead to a developmental and degenerative epileptic-dyskinetic encephalopathy.Human mutation · 2020Article
- Review
- Physiological responses and proteomic changes reveal insights into Stylosanthes response to manganese toxicity.BMC plant biology · 2019Article
- Sensing and signaling mechanisms linking dietary methionine restriction to the behavioral and physiological components of the response.Frontiers in neuroendocrinology · 2018Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
The eukaryotic elongation factor 1A (eEF1A) delivers aminoacyl-tRNAs to the ribosomal A-site during protein synthesis. To ensure a continuous supply of amino acids, cells harbor the kinase Gcn2 and its effector protein Gcn1. The ultimate signal for amino acid shortage is uncharged tRNAs. We have proposed a model for sensing starvation, in which Gcn1 and Gcn2 are tethered to the ribosome, and Gcn1 is directly involved in delivering uncharged tRNAs from the A-site to Gcn2 for its subsequent activation. Gcn1 and Gcn2 are large proteins, and these proteins as well as eEF1A access the A-site, leading us to investigate whether there is a functional or physical link between these proteins. Using Saccharomyces cerevisiae cells expressing His(6)-eEF1A and affinity purification, we found that eEF1A co-eluted with Gcn2. Furthermore, Gcn2 co-immunoprecipitated with eEF1A, suggesting that they reside in the same complex. The purified GST-tagged Gcn2 C-terminal domain (CTD) was sufficient for precipitating eEF1A from whole cell extracts generated from gcn2Δ cells, independently of ribosomes. Purified GST-Gcn2-CTD and purified His(6)-eEF1A interacted with each other, and this was largely independent of the Lys residues in Gcn2-CTD known to be required for tRNA binding and ribosome association. Interestingly, Gcn2-eEF1A interaction was diminished in amino acid-starved cells and by uncharged tRNAs in vitro, suggesting that eEF1A functions as a Gcn2 inhibitor. Consistent with this possibility, purified eEF1A reduced the ability of Gcn2 to phosphorylate its substrate, eIF2α, but did not diminish Gcn2 autophosphorylation. These findings implicate eEF1A in the intricate regulation of Gcn2 and amino acid homeostasis.
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Registered trials
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