ArticleeLife2020
Misfolded proteins bind and activate death receptor 5 to trigger apoptosis during unresolved endoplasmic reticulum stress.
Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
What it found
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The trial behind it
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Who cites it
82 citing papers in PubMed, 128 citations in OpenAlex.
- Prognostic Value of Endoplasmic Reticulum Stress-Related Gene Signature in Thyroid Cancer.Current medical science · 2026Article
- A DR5/Ligase 3-mediated feedback loop perpetuates immunogenicity in mismatch repair deficient colorectal cancer.Gastroenterology · 2026Article
- Inhibition of SIK2 and SIK3 induces adaptive ER-phagy and creates a therapeutic vulnerability in ovarian cancer.Research square · 2026Article
- IRE1-XBP1driven induction of TMED9 stabilizes ATF6 during ER stress to promote cell survival.Cellular & molecular biology letters · 2026Article
- REDD1/DDIT4 counteracts endoplasmic reticulum stress-induced apoptosis by controlling the expression of death receptor TRAILR2/DR5 in cancer cells.Cell death & disease · 2026Article
- BIP orchestrates bidirectional ER protein trafficking via co-chaperone complexes.Cellular & molecular biology letters · 2026Article
- A New Perspective on Osteogenesis Imperfecta: From Cellular Mechanisms to the Systemic Impact of Collagen Dysfunction.International journal of molecular sciences · 2026Review
- Demethylzeylasteral alleviates myeloid leukemia through PERK/eIF2α/ATF4/CHOP-mediated cell apoptosis.Translational cancer research · 2025Article
- The Central Role of NRF2 in Cancer Metabolism and Redox Signaling: Novel Insights into Crosstalk with ER Stress and Therapeutic Modulation.Cell biochemistry and biophysics · 2025Review
- Targeting proteostasis for cancer therapy: current advances, challenges, and future perspectives.Molecular cancer · 2025Review
- Deciphering the determinants of recombinant protein expression across the human secretome.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Raphin-1 mediates the survival and sensitivity to radiation of pediatric-type diffuse high-grade glioma via phosphorylated eukaryotic initiation factor 2α-dependent and -independent processes.Molecular oncology · 2025Article
- Ribosomal RNA Degradation (RNA Disruption) in Tumour Cells: Mechanistic Insights and Potential Clinical Utility.Cancers · 2025Review
- Toxicological Mechanisms of Uranium-Induced Apoptosis in HK-2 Cells: A Proteomics and Metabolomics Study.Toxics · 2025Article
- Activation of the integrated stress response and loss of cFLIPCell death discovery · 2025Article
- DR5 Disulfide Bonding Functions as a Sensor and Effector of Protein Folding Stress.Molecular cancer research : MCR · 2025Article
- Liposome-Polymer Nanoparticles Loaded with Copper Diethyldithiocarbamate and 6-Bromo-Indirubin-3'-Oxime Enable the Treatment of Refractive Melanoma.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- Endoplasmic Reticulum Stress in Tuberculosis: Molecular Bases and Pathophysiological Implications in the Immunopathogenesis of the Disease.International journal of molecular sciences · 2025Review
- TRAF3IP3 Induces ER Stress-Mediated Apoptosis with Protective Autophagy to Inhibit Lung Adenocarcinoma Proliferation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Expanded Phenotype of theCells · 2025Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Disruption of protein folding in the endoplasmic reticulum (ER) activates the unfolded protein response (UPR)-a signaling network that ultimately determines cell fate. Initially, UPR signaling aims at cytoprotection and restoration of ER homeostasis; that failing, it drives apoptotic cell death. ER stress initiates apoptosis through intracellular activation of death receptor 5 (DR5) independent of its canonical extracellular ligand Apo2L/TRAIL; however, the mechanism underlying DR5 activation is unknown. In cultured human cells, we find that misfolded proteins can directly engage with DR5 in the ER-Golgi intermediate compartment, where DR5 assembles pro-apoptotic caspase 8-activating complexes. Moreover, peptides used as a proxy for exposed misfolded protein chains selectively bind to the purified DR5 ectodomain and induce its oligomerization. These findings indicate that misfolded proteins can act as ligands to activate DR5 intracellularly and promote apoptosis. We propose that cells can use DR5 as a late protein-folding checkpoint before committing to a terminal apoptotic fate.
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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.