ArticleFEBS open bio2022
A systems biological analysis of the ATF4-GADD34-CHOP regulatory triangle upon endoplasmic reticulum stress.
Article in FEBS open bio, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 26 citations in OpenAlex.
- Article
- Single-nuclei UPR profiling by flow cytometry reveals bortezomib resistance mechanisms in multiple myeloma.EMBO molecular medicine · 2026Article
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- Epigallocatechin gallate attenuates free fatty acid-induced hepatocyte apoptosis by restoring endoplasmic reticulum homeostasis.Veterinary research communications · 2026Article
- Article
- Overcoming immunotherapy resistance in breast cancer: a novel strategy by targeting the integrated stress response.Frontiers in cell and developmental biology · 2026Review
- Resveratrol-Supported Bioenergetics Leads to Higher Productivity and Accompanying Endoplasmic Reticulum Stress in a mAb-Producing CHO Cell Line.International journal of molecular sciences · 2025Article
- Review
- Mitochondrial subtypes in renal ischemia reperfusion injury guide delayed graft function and Long-Term graft prediction.Scientific reports · 2025Article
- Review
- SEC24D depletion induces osteogenic differentiation deficiency by inactivating the ATF6/TGF-β/Runx2 regulatory loop.Communications biology · 2025Article
- Mixed lineage kinase domain-like protein deficiency exacerbates early injury in a mouse model of acetaminophen hepatotoxicity.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Impact of ER stress and the unfolded protein response on Fabry disease.EBioMedicine · 2025Review
- C/EBP Homologous Protein Expression in Retinal Ganglion Cells Induces Neurodegeneration in Mice.International journal of molecular sciences · 2025Article
- Protein phosphatase 1 regulatory subunit 15 A (PPP1R15A) promoted the progression of gastric cancer by activating cell autophagy under energy stress.Journal of experimental & clinical cancer research : CR · 2025Article
- Endoplasmic Reticulum Stress in Cancer Progression: A Comprehensive Review of Its Role and Mechanisms.International journal of medical sciences · 2025Review
- Tribbles pseudokinase 3 promoted renal fibrosis by regulating the expression of DNA damage-inducible transcript 3 in diabetic nephropathy.Biomolecules & biomedicine · 2024Article
- Article
- Analysis of Toxic Effects of Fluoride on Ovine Follicular Granulosa Cells Using RNA-Seq.Antioxidants (Basel, Switzerland) · 2024Article
- Mechanism of Decision Making between Autophagy and Apoptosis Induction upon Endoplasmic Reticulum Stress.International journal of molecular sciences · 2024Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endoplasmic reticulum (ER) stress-dependent accumulation of incorrectly folded proteins leads to activation of the unfolded protein response. The role of the unfolded protein response (UPR) is to avoid cell damage and restore the homeostatic state by autophagy; however, excessive ER stress results in apoptosis. Here we investigated the ER stress-dependent feedback loops inside one of the UPR branches by focusing on PERK-induced ATF4 and its two targets, called CHOP and GADD34. Our goal was to qualitatively describe the dynamic behavior of the system by exploring the key regulatory motifs using both molecular and theoretical biological techniques. Using the HEK293T cell line as a model system, we confirmed that the life-or-death decision is strictly regulated. We investigated the dynamic characteristics of the crucial elements of the PERK pathway at both the RNA and protein level upon tolerable and excessive levels of ER stress. Of particular note, inhibition of GADD34 or CHOP resulted in various phenotypes upon high levels of ER stress. Our computer simulations suggest the existence of two new feedback loops inside the UPR. First, GADD34 seems to have a positive effect on ATF4 activity, while CHOP inhibits it. We claim that these newly described feedback loops ensure the fine-tuning of the ATF4-dependent stress response mechanism of the cell.
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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.