ArticleJournal of cell science2013
Coordinate regulation of eIF2α phosphorylation by PPP1R15 and GCN2 is required during Drosophila development.
Article in Journal of cell science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 54 citations in OpenAlex.
- GCN2 in proteostasis: structural logic, signalling networks and disease.The FEBS journal · 2026Review
- Spalt-related is an inhibitor of mTORC1-mediated growth activated by the integrated stress response.The EMBO journal · 2026Article
- Targeting the integrated stress response or Ataxin-2 alleviates neurodegeneration in PolyGR models of C9orf72 associated frontotemporal dementia and amyotrophic lateral sclerosis.Acta neuropathologica communications · 2026Article
- The interaction between GCN2 and eIF2 mediates the resistance of cotton bollworm to the Bacillus thuringiensis Cry1Ac toxin.PLoS pathogens · 2025Article
- Article
- Circadian Control of Protein Synthesis.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- A novel human fetal lung-derived alveolar organoid model reveals mechanisms of surfactant protein C maturation relevant to interstitial lung disease.The EMBO journal · 2025Article
- Evaluation of Eukaryotic mRNA Coding Potential.Methods in molecular biology (Clifton, N.J.) · 2025Article
- eIF2α phosphorylation evokes dystonia-like movements with D2-receptor and cholinergic origin and abnormal neuronal connectivity.bioRxiv : the preprint server for biology · 2024Article
- Collective cell migration relies on PPP1R15-mediated regulation of the endoplasmic reticulum stress response.Current biology : CB · 2024Article
- Substrate recruitment via eIF2γ enhances catalytic efficiency of a holophosphatase that terminates the integrated stress response.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The PPP1R15 Family of eIF2-alpha Phosphatase Targeting Subunits (GADD34 and CReP).International journal of molecular sciences · 2023Review
- GCN2 mediates access to stored amino acids for somatic maintenance duringbioRxiv : the preprint server for biology · 2023Article
- A novel human fetal lung-derived alveolar organoid model reveals mechanisms of surfactant protein C maturation relevant to interstitial lung disease.bioRxiv : the preprint server for biology · 2023Article
- Loss of Paip1 causes translation reduction and induces apoptotic cell death through ISR activation and Xrp1.Cell death discovery · 2023Article
- Intestinal GCN2 controlseLife · 2023Article
- The small compound Icerguastat reduces muscle defects in oculopharyngeal muscular dystrophy through the PERK pathway of the unfolded protein response.Open biology · 2023Article
- Sensing of the non-essential amino acid tyrosine governs the response to protein restriction in Drosophila.Nature metabolism · 2022Article
- New Drosophila models to uncover the intrinsic and extrinsic factors that mediate the toxicity of the human prion protein.Disease models & mechanisms · 2022Article
- Article
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9 authors at 2 institutions in 1 country.
Funding
Abstract
Phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α) by the kinase GCN2 attenuates protein synthesis during amino acid starvation in yeast, whereas in mammals a family of related eIF2α kinases regulate translation in response to a variety of stresses. Unlike single-celled eukaryotes, mammals also possess two specific eIF2α phosphatases, PPP1R15a and PPP1R15b, whose combined deletion leads to a poorly understood early embryonic lethality. We report the characterisation of the first non-mammalian eIF2α phosphatase and the use of Drosophila to dissect its role during development. The Drosophila protein demonstrates features of both mammalian proteins, including limited sequence homology and association with the endoplasmic reticulum. Of note, although this protein is not transcriptionally regulated, its expression is controlled by the presence of upstream open reading frames in its 5'UTR, enabling induction in response to eIF2α phosphorylation. Moreover, we show that its expression is necessary for embryonic and larval development and that this is to oppose the inhibitory effects of GCN2 on anabolic growth.
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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.