ReviewBiochemical Society transactions2019
Towards a model of GCN2 activation.
Review in Biochemical Society transactions, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
79 citing papers in PubMed, 153 citations in OpenAlex.
- Gut microbial signatures in poultry under low-protein diets and lysine restriction: implications for precision nutrition.Veterinary and animal science · 2026Review
- White matter disorders at the intersection of transcription, RNA processing and translation.Nature reviews. Neurology · 2026Review
- GCN2 in proteostasis: structural logic, signalling networks and disease.The FEBS journal · 2026Review
- Autophagy and metabolic homeostasis: Exploration in obesity‑related metabolic diseases (Review).International journal of molecular medicine · 2026Review
- Acid ceramidase inhibition enhances BCL-2 targeting in venetoclax-resistant acute myeloid leukemia.Blood neoplasia · 2026Article
- A Novel Potent and Selective GCN2 Inhibitor, APL-4098, Has Antileukemic Activity through Dysregulation of Mitochondrial Function.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- The regulation, function and disease relevance of cytoplasmic tRNAs.Nature reviews. Molecular cell biology · 2026Review
- 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
- The integrated stress response in pancreatic β-cell failure in diabetes: from molecular mechanisms to precision therapeutics.Frontiers in endocrinology · 2026Review
- Noncoding RNAs: The Not So "Junk" DNA Is the Blueprint of the Transcriptional Landscape of the RNA World.Experientia supplementum (2012) · 2026Review
- The dual role of ATF4 in neurons: from stress adaptation to therapeutic intervention.Frontiers in molecular neuroscience · 2026Review
- Transfer RNA regulation during herpesvirus infection: Wielding a sword or raising a shield?PLoS pathogens · 2025Article
- RAF inhibitors activate the integrated stress response by direct activation of GCN2.Nature communications · 2025Article
- Differential cell survival outcomes in response to diverse amino acid stress.Life science alliance · 2025Article
- mTORC1 senses glutamine and other amino acids through GCN2.The EMBO journal · 2025Article
- The ATF4-glutamine axis: a central node in cancer metabolism, stress adaptation, and therapeutic targeting.Cell death discovery · 2025Review
- Insights into the role of collided ribosomes during the activation of the integrated stress response.Biochemical Society transactions · 2025Review
- Arginine promotes the activation of human lung fibroblasts independent of its metabolism.The Biochemical journal · 2025Article
- Hog1/p38 regulates the integrated stress response (ISR) and global transcriptomic changes inbioRxiv : the preprint server for biology · 2025Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
Cells must be able to sense and adapt to their surroundings to thrive in a dynamic environment. Key to adapting to a low nutrient environment is the Integrated Stress Response (ISR), a short-lived pathway that allows cells to either regain cellular homeostasis or facilitate apoptosis during periods of stress. Central to the ISR is the protein kinase General Control Non-depressible 2 (GCN2), which is responsible for sensing starvation. Upon amino acid deficiency, GCN2 is activated and initiates the ISR by phosphorylating the translation initiation factor eIF2α, stalling protein translation, and activating the transcription factor ATF4, which in turn up-regulates autophagy and biosynthesis pathways. A key outstanding question is how GCN2 is activated from an autoinhibited state. Until recently, a model of activation focussed on the increase of deacylated tRNA associated with amino acid starvation, with deacylated tRNA binding directly to GCN2 and releasing autoinhibition. However, in vivo experiments have pointed towards an alternative, deacylated-tRNA-independent mechanism of activation. Here, we review the various factors that may facilitate GCN2 activation, including recent research showing that the P-stalk complex, a ribosome-associated heteropentameric protein complex, is a potent activator of GCN2.
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Registered trials
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.