ArticleCell reports2017
The GCN2-ATF4 Signaling Pathway Induces 4E-BP to Bias Translation and Boost Antimicrobial Peptide Synthesis in Response to Bacterial Infection.
Article in Cell reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- 4EHP and NELF-E regulate physiological ATF4 induction and proteostasis in disease models of Drosophila.Nature communications · 2025Article
- The GCN-2/eIF-2α/ATF-4 signaling pathway is involved inVirulence · 2025Article
- Decanoic acid extends lifespan and modulates metabolism in models of PLA2G6-associated neurodegeneration.Disease models & mechanisms · 2025Article
- The integrated stress response suppresses antiviral RNA interference by autophagy-mediated degradation of the RNA-induced silencing complex.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Emerging roles for integrated stress response signaling in homeostasis.The FEBS journal · 2025Review
- The translational inhibitor 4EBP/Thor is required for Drosophila adaptation to hypoxia.Scientific reports · 2025Article
- Diverse roles of stress-responsive RNP granules in oogenesis and infertility.Biology of reproduction · 2025Review
- High sugar diets can increase susceptibility to bacterial infection in Drosophila melanogaster.PLoS pathogens · 2024Article
- Insulin receptor orchestrates kidney antibacterial defenses.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Intestinal GCN2 controlseLife · 2023Article
- Regulating metabolism to shape immune function: Lessons from Drosophila.Seminars in cell & developmental biology · 2023Review
- Multiple Roles of the Stress Sensor GCN2 in Immune Cells.International journal of molecular sciences · 2023Review
- The Insulin Receptor and Insulin like Growth Factor Receptor 5' UTRs Support Translation Initiation Independently of EIF4G1.Molecular and cellular biology · 2023Article
- Interactions between innate immunity and insulin signaling affect resistance to infection in insects.Frontiers in immunology · 2023Review
- Mitochondrial remodelling is essential for female germ cell differentiation and survival.PLoS genetics · 2023Article
- New Drosophila models to uncover the intrinsic and extrinsic factors that mediate the toxicity of the human prion protein.Disease models & mechanisms · 2022Article
- A protein-trap allele reveals roles for Drosophila ATF4 in photoreceptor degeneration, oogenesis and wing development.Disease models & mechanisms · 2022Article
- Drosophila Unfolded Protein Response (UPR) Assays In Vitro and In Vivo.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Impaired skeletal muscle hypertrophy signaling and amino acid deprivation response in Apoe knockout mice with an unhealthy lipoprotein distribution.Scientific reports · 2021Article
- Reovirus and the Host Integrated Stress Response: On the Frontlines of the Battle to Survive.Viruses · 2021Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Bacterial infection often leads to suppression of mRNA translation, but hosts are nonetheless able to express immune response genes through as yet unknown mechanisms. Here, we use a Drosophila model to demonstrate that antimicrobial peptide (AMP) production during infection is paradoxically stimulated by the inhibitor of cap-dependent translation, 4E-BP (eIF4E-binding protein; encoded by the Thor gene). We found that 4E-BP is induced upon infection with pathogenic bacteria by the stress-response transcription factor ATF4 and its upstream kinase, GCN2. Loss of gcn2, atf4, or 4e-bp compromised immunity. While AMP transcription is unaffected in 4e-bp mutants, AMP protein levels are substantially reduced. The 5' UTRs of AMPs score positive in cap-independent translation assays, and this cap-independent activity is enhanced by 4E-BP. These results are corroborated in vivo using transgenic 5' UTR reporters. These observations indicate that ATF4-induced 4e-bp contributes to innate immunity by biasing mRNA translation toward cap-independent mechanisms, thus enhancing AMP synthesis.
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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.