ArticleNature chemical biology2022
GCN2 kinase activation by ATP-competitive kinase inhibitors.
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 36 papers.
What it found
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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.
The trial behind it
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
36 citing papers in PubMed, 54 citations in OpenAlex.
- GCN2 in proteostasis: structural logic, signalling networks and disease.The FEBS journal · 2026Review
- Unraveling competitive protein interactions: A critical step toward improved production and therapeutics.Journal of advanced research · 2026Review
- An inhibitor of GCN2 and the integrated stress response directly targets ZAK protein kinase to limit cytotoxicity.The Journal of biological chemistry · 2026Article
- TSC2 is a stress granule suppressor.bioRxiv : the preprint server for biology · 2026Article
- Elevated GCN2 levels in cancer cells confer protection from mitotic stress and faster cell movement.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- A Chemical-Genetic Interaction Matrix Reveals Drug Mechanism and Genetic Architecture.bioRxiv : the preprint server for biology · 2026Article
- Redox-metabolic circuits as a central regulator of T cell-based immunotherapy.Frontiers in immunology · 2026Review
- GCN2 in Cancer: Molecular Mechanisms to Therapeutic Potential.Current cancer drug targets · 2026Review
- WEE1 inhibitors trigger GCN2-mediated activation of the integrated stress response.Nature communications · 2025Article
- RAF inhibitors activate the integrated stress response by direct activation of GCN2.Nature communications · 2025Article
- WEE1 inhibitors synergise with mRNA translation defects via activation of the kinase GCN2.Nature communications · 2025Article
- Inhibition of dimeric SARS-CoV-2 Mpro displays positive cooperativity and a mixture of covalent and non-covalent binding.iScience · 2025Article
- Ribosome association inhibits stress-induced gene mRNA localization to stress granules.Genes & development · 2025Article
- De Novo Serine Synthesis Is a Metabolic Vulnerability That Can Be Exploited to Overcome Sunitinib Resistance in Advanced Renal Cell Carcinoma.Cancer research · 2025Article
- Targeting PKC as a Therapeutic Strategy to Overcome Chemoresistance in TNBC by Restoring Aurora Kinase B Expression.Journal of cellular and molecular medicine · 2025Article
- The protein kinases family in fungi: adaptability, virulence and conservation between species.Frontiers in microbiology · 2025Review
- BRAFbioRxiv : the preprint server for biology · 2024Article
- Ferroptosis - a potential feature underlying neratinib-induced colonic epithelial injury.Cancer chemotherapy and pharmacology · 2024Article
- GCN2 is a determinant of the response to WEE1 kinase inhibition in small-cell lung cancer.Cell reports · 2024Article
- Functional validation of EIF2AK4 (GCN2) missense variants associated with pulmonary arterial hypertension.Human molecular genetics · 2024Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Small-molecule kinase inhibitors represent a major group of cancer therapeutics, but tumor responses are often incomplete. To identify pathways that modulate kinase inhibitor response, we conducted a genome-wide knockout (KO) screen in glioblastoma cells treated with the pan-ErbB inhibitor neratinib. Loss of general control nonderepressible 2 (GCN2) kinase rendered cells resistant to neratinib, whereas depletion of the GADD34 phosphatase increased neratinib sensitivity. Loss of GCN2 conferred neratinib resistance by preventing binding and activation of GCN2 by neratinib. Several other Food and Drug Administration (FDA)-approved inhibitors, such erlotinib and sunitinib, also bound and activated GCN2. Our results highlight the utility of genome-wide functional screens to uncover novel mechanisms of drug action and document the role of the integrated stress response (ISR) in modulating the response to inhibitors of oncogenic kinases.
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What OpenQuestion holds
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.