ArticleeLife2019
The ribosomal P-stalk couples amino acid starvation to GCN2 activation in mammalian cells.
Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
107 citing papers in PubMed, 174 citations in OpenAlex.
- Impact of basal media and feeds on CHO cell cultures: a full factorial experiment implicating tryptophan in medium-feed antagonism.Bioprocess and biosystems engineering · 2026Article
- Review
- Substrate Binding Relieves Autoinhibition of the Mammalian GCN2 Kinase.bioRxiv : the preprint server for biology · 2026Article
- GCN2 in proteostasis: structural logic, signalling networks and disease.The FEBS journal · 2026Review
- Allosteric disordering of eIF2B regulates the integrated stress response.Nature chemical biology · 2026Article
- Metabolite import by SLC33A1 is required for ATF6 activation during endoplasmic reticulum stress.Life science alliance · 2026Article
- tRNA synthetase activity is required for stress granule and P-body assembly.Genes & development · 2026Article
- Quality control and signaling pathways at stalled ribosomes.Experimental & molecular medicine · 2026Review
- GCN2 in Cancer: Molecular Mechanisms to Therapeutic Potential.Current cancer drug targets · 2026Review
- GCN2 regulates paclitaxel-induced neuropathic pain.British journal of pharmacology · 2025Article
- Depurination of sarcin/ricin loop 25S rRNA is signaled through the small ribosomal subunit during translation.RNA (New York, N.Y.) · 2025Article
- Article
- WEE1 inhibitors synergise with mRNA translation defects via activation of the kinase GCN2.Nature communications · 2025Article
- Insights into the role of collided ribosomes during the activation of the integrated stress response.Biochemical Society transactions · 2025Review
- Translation suppresses exogenous target RNA-mediated microRNA decay.Nature communications · 2025Article
- Structure of a Gcn2 dimer in complex with the large 60S ribosomal subunit.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- RNF10 and RIOK3 facilitate 40S ribosomal subunit degradation upon 60S biogenesis disruption or amino acid starvation.Cell reports · 2025Article
- Transfer RNA acetylation regulates in vivo mammalian stress signaling.Science advances · 2025Article
- Glycyl-tRNA sequestration is a unifying mechanism underlying GARS1-associated peripheral neuropathy.Nucleic acids research · 2025Article
- eEF2K regulates pain through translational control of BDNF.Molecular cell · 2025Article
47 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The eukaryotic translation initiation factor 2α (eIF2α) kinase GCN2 is activated by amino acid starvation to elicit a rectifying physiological program known as the Integrated Stress Response (ISR). A role for uncharged tRNAs as activating ligands of yeast GCN2 is supported experimentally. However, mouse GCN2 activation has recently been observed in circumstances associated with ribosome stalling with no global increase in uncharged tRNAs. We report on a mammalian CHO cell-based CRISPR-Cas9 mutagenesis screen for genes that contribute to ISR activation by amino acid starvation. Disruption of genes encoding components of the ribosome P-stalk, uL10 and P1, selectively attenuated GCN2-mediated ISR activation by amino acid starvation or interference with tRNA charging without affecting the endoplasmic reticulum unfolded protein stress-induced ISR, mediated by the related eIF2α kinase PERK. Wildtype ribosomes isolated from CHO cells, but not those with P-stalk lesions, stimulated GCN2-dependent eIF2α phosphorylation in vitro. These observations support a model whereby lack of a cognate charged tRNA exposes a latent capacity of the ribosome P-stalk to activate GCN2 in cells and help explain the emerging link between ribosome stalling and ISR activation.
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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.