ArticleMolecular and cellular biology2006
Autocrine tumor necrosis factor alpha links endoplasmic reticulum stress to the membrane death receptor pathway through IRE1alpha-mediated NF-kappaB activation and down-regulation of TRAF2 expression.
Article in Molecular and cellular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 375 papers.
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Who cites it
375 citing papers in PubMed, 741 citations in OpenAlex.
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- Dietary Saturated Fatty Acids as Evolutionarily Conserved Signals of Immune Activation.DNA and cell biology · 2026Review
- The role of 2-Oxoglutarate dehydrogenase complex mitochondrial enzyme in alzheimer's disease: a literature review and bioinformatics workflow.Metabolic brain disease · 2026Review
- Brucella Omp25 activates the unfolded protein response to promote intracellular proliferation and inflammation.The Journal of biological chemistry · 2026Article
- Inhibition of α-1,3-mannosyltransferase sensitizes head and neck squamous cell carcinomas to cetuximab via endoplasmic reticulum stress.Cell stress & chaperones · 2026Article
- From stress to homeostasis: Mass spectrometry-based insights into the unfolded protein response (UPR) and proteostasis.Advances in biological regulation · 2026Review
- A systematic review on the potential of modulating the IRE arm of the UPR in U87 and U251 glioblastoma cells for improved therapeutic efficacy.Molecular biology research communications · 2026Review
- The IRE1α Pathway Links Endoplasmic Reticulum Stress to Atherosclerosis-Related Inflammation and Lipid Accumulation.Mediators of inflammation · 2026Article
- FoxO3a-Mediated Modulation of PD-L1 Expression and Inhibition by Dihydroartemisinin in Triple-Negative Breast Cancer.Journal of cellular and molecular medicine · 2026Article
- Sphingolipid-Neuroinflammation Axis in Parkinson's Disease: Focus on S1P/SPHK1-NF‑κB Signaling.Journal of inflammation research · 2026Review
- The IRE1Cell stress · 2026Article
- Comparative Protective Effects of ATP and TPP Against Olaparib-Induced Ovarian Injury in Rats: Insights from Biochemical Parameters, Histopathology, and IRE1α, Cleaved Caspase-3, LC3B, and NF-κB p65 Double Immunofluorescence.Drug design, development and therapy · 2026Article
- Aging and lung diseases: Unraveling mechanisms and therapeutic targets.Chinese medical journal pulmonary and critical care medicine · 2025Review
- Endoplasmic reticulum stress at the forefront of fatty liver diseases and cancer.Pharmacological reviews · 2025Review
- Metformin Mitigates the Impact of Arsenic Exposure on the Maternal and Offspring Reproductive System of Female Mice.Biological trace element research · 2025Article
- Diabetes mellitus and the key role of endoplasmic reticulum stress in pancreatic β cells.Nature reviews. Endocrinology · 2025Review
- Dihydromyricetin protects hippocampal neurons in sepsis-associated encephalopathy by reducing ER stress-mediated apoptosis and inflammation.Journal of molecular histology · 2025Article
- The interplay between endoplasmic reticulum stress and inflammation in multiple sclerosis.Scientific reports · 2025Article
- Endoplasmic Reticulum Stress and Unfolded Protein Response Sensor ERN1 Regulates Organic Dust Induction of Lung Inflammation.FASEB bioAdvances · 2025Article
315 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
NF-kappaB is critical for determining cellular sensitivity to apoptotic stimuli by regulating both mitochondrial and death receptor apoptotic pathways. The endoplasmic reticulum (ER) emerges as a new apoptotic signaling initiator. However, the mechanism by which ER stress activates NF-kappaB and its role in regulation of ER stress-induced cell death are largely unclear. Here, we report that, in response to ER stress, IKK forms a complex with IRE1alpha through the adapter protein TRAF2. ER stress-induced NF-kappaB activation is impaired in IRE1alpha knockdown cells and IRE1alpha(-/-) MEFs. We found, however, that inhibiting NF-kappaB significantly decreased ER stress-induced cell death in a caspase-8-dependent manner. Gene expression analysis revealed that ER stress-induced expression of tumor necrosis factor alpha (TNF-alpha) was IRE1alpha and NF-kappaB dependent. Blocking TNF receptor 1 signaling significantly inhibited ER stress-induced cell death. Further studies suggest that ER stress induces down-regulation of TRAF2 expression, which impairs TNF-alpha-induced activation of NF-kappaB and c-Jun N-terminal kinase and turns TNF-alpha from a weak to a powerful apoptosis inducer. Thus, ER stress induces two signals, namely TNF-alpha induction and TRAF2 down-regulation. They work in concert to amplify ER-initiated apoptotic signaling through the membrane death receptor.
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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.