ArticleNature cell biology2012
Toll-like receptor activation suppresses ER stress factor CHOP and translation inhibition through activation of eIF2B.
Article in Nature cell biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
What it found
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Who cites it
81 citing papers in PubMed, 127 citations in OpenAlex.
- Early life stress-induced depression reveals distinct region-specific modulation of unfolded protein response genes in the prefrontal cortex and hippocampus of rats.Frontiers in psychiatry · 2026Article
- LPS-TLR4 signaling attenuates CHOP-mediated apoptosis under endoplasmic reticulum stress conditions during porcine embryonic development.Frontiers in cell and developmental biology · 2026Article
- Pattern recognition receptors: function, regulation and therapeutic potential.Signal transduction and targeted therapy · 2025Review
- Endoplasmic reticulum stress triggers unfolded protein response as an antiviral strategy of teleost erythrocytes.Frontiers in immunology · 2024Article
- TRIF-dependent signaling and its role in liver diseases.Frontiers in cell and developmental biology · 2024Review
- Control of Selective mRNA Translation in Neuronal Subcellular Compartments in Health and Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Review
- Toll-like receptors 2 and 4 stress signaling and sodium-glucose cotransporter-2 in kidney disease.Molecular and cellular biochemistry · 2023Review
- The unfolded protein response to PI*Z alpha-1 antitrypsin in human hepatocellular and murine models.Hepatology communications · 2022Article
- Sex differences in α-adrenergic receptor function contribute to impaired hypothalamic metaplasticity following chronic intermittent ethanol exposure.Alcoholism, clinical and experimental research · 2022Article
- Exosomes from Human Placenta Choriodecidual Membrane-Derived Mesenchymal Stem Cells Mitigate Endoplasmic Reticulum Stress, Inflammation, and Lung Injury in Lipopolysaccharide-Treated Obese Mice.Antioxidants (Basel, Switzerland) · 2022Article
- WLS/wntless is essential in controlling dendritic cell homeostasis via a WNT signaling-independent mechanism.Autophagy · 2021Article
- Effectors Targeting the Unfolded Protein Response during Intracellular Bacterial Infection.Microorganisms · 2021Review
- The UPR sensor IRE1α promotes dendritic cell responses to control Toxoplasma gondii infection.EMBO reports · 2021Article
- Proteostasis in dendritic cells is controlled by the PERK signaling axis independently of ATF4.Life science alliance · 2021Article
- Proteostasis Dysfunction in Aged Mammalian Cells. The Stressful Role of Inflammation.Frontiers in molecular biosciences · 2021Review
- Bacterial Manipulation of the Integrated Stress Response: A New Perspective on Infection.Frontiers in microbiology · 2021Review
- The ER Stress/UPR Axis in Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis.Life (Basel, Switzerland) · 2020Review
- The integrated stress response in pulmonary disease.European respiratory review : an official journal of the European Respiratory Society · 2020Review
- Mechanisms, regulation and functions of the unfolded protein response.Nature reviews. Molecular cell biology · 2020Review
- Article
21 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
4 authors at 2 institutions in 1 country.
Funding
Abstract
Activation of Toll-like receptors (TLRs) induces the endoplasmic reticulum (ER) unfolded protein response (UPR) to accommodate essential protein translation. However, despite increased levels of phosphorylated eIF2α (p-eIF2α), a TLR-TRIF-dependent pathway assures that the cells avoid CHOP induction, apoptosis and translational suppression of critical proteins. As p-eIF2α decreases the functional interaction of eIF2 with eIF2B, a guanine nucleotide exchange factor (GEF), we explored the hypothesis that TLR-TRIF signalling activates eIF2B GEF activity to counteract the effects of p-eIF2α. We now show that TLR-TRIF signalling activates eIF2B GEF through PP2A-mediated serine dephosphorylation of the eIF2B ɛ-subunit. PP2A itself is activated by decreased Src-family-kinase-induced tyrosine phosphorylation of its catalytic subunit. Each of these processes is required for TLR-TRIF-mediated CHOP suppression in ER-stressed cells in vitro and in vivo. Thus, in the setting of prolonged, physiologic ER stress, a unique TLR-TRIF-dependent translational control pathway enables cells to carry out essential protein synthesis and avoid CHOP-induced apoptosis while still benefiting from the protective arms of the UPR.
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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.