ArticleCell death & disease2018
c-Jun N-terminal kinases differentially regulate TNF- and TLRs-mediated necroptosis through their kinase-dependent and -independent activities.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 59 citations in OpenAlex.
- Periostin-CCL3 Feedforward Signaling Loop Promotes Cardiac Fibrosis and Cardiomyocyte Necroptosis in Arrhythmogenic Cardiomyopathy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Proteomic and Transcriptomic Signatures of Poor Asthma Symptom Control in the U-BIOPRED Cohort.Allergy · 2026Article
- The RIPK3 Inhibitor GSK872 Attenuates Inflammation and Necroptosis via Modulation of the JNK Signaling Pathway in LPS-Stimulated Microglia.Biomolecules & therapeutics · 2026Article
- Identification of the Role of Necroptosis-Related Genes in the Oxidative Damage of Lens Epithelial Cells and Validation in Ultraviolet B-induced Cataract in Rats.Combinatorial chemistry & high throughput screening · 2026Article
- The Role of Traditional Chinese Medicine in Acute Lung Injury: Targeting Programmed Cell Death.Drug design, development and therapy · 2026Review
- Induction of hyperlipidemic pancreatitis by different fatty acids: A narrative review.World journal of gastroenterology · 2025Review
- Identification of potential therapeutic targets from bioinformatics analysis of necroptosis and immune infiltration in acute myocardial infarction.Journal of cardiothoracic surgery · 2024Article
- Targeting necroptosis: a promising avenue for respiratory disease treatment.Cell communication and signaling : CCS · 2024Review
- RIP3 in Necroptosis: Underlying Contributions to Traumatic Brain Injury.Neurochemical research · 2024Review
- Neutrophil extracellular traps aggravate intestinal epithelial necroptosis in ischaemia-reperfusion by regulating TLR4/RIPK3/FUNDC1-required mitophagy.Cell proliferation · 2024Article
- The dance of macrophage death: the interplay between the inevitable and the microenvironment.Frontiers in immunology · 2024Review
- Tumor-produced immune regulatory factors as a therapeutic target in cancer treatment.Frontiers in immunology · 2024Review
- Comprehensive analysis of mitochondrial dysfunction and necroptosis in intracranial aneurysms from the perspective of predictive, preventative, and personalized medicine.Apoptosis : an international journal on programmed cell death · 2023Article
- Pazopanib alleviates neuroinflammation and protects dopaminergic neurons in LPS-stimulated mouse model by inhibiting MEK4-JNK-AP-1 pathway.Acta pharmacologica Sinica · 2023Article
- RIPK3 promoter hypermethylation in hepatocytes protects from bile acid-induced inflammation and necroptosis.Cell death & disease · 2023Article
- Analysis of necroptosis-related prognostic genes and immune infiltration in idiopathic pulmonary fibrosis.Frontiers in immunology · 2023Article
- Frizzled-6 promotes hematopoietic stem/progenitor cell mobilization and survival during LPS-induced emergency myelopoiesis.Stem cell reports · 2022Article
- The regulation of necroptosis and perspectives for the development of new drugs preventing ischemic/reperfusion of cardiac injury.Apoptosis : an international journal on programmed cell death · 2022Review
- Exploring the Role ofToxins · 2022Review
- Mechanism of Bile Acid-Induced Programmed Cell Death and Drug Discovery against Cancer: A Review.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor necrosis factor (TNF) and Toll-like receptor (TLR)3/TLR4 activation trigger necroptotic cell death through downstream signaling complex containing receptor-interacting protein kinase 1 (RIPK1), RIPK3, and pseudokinase mixed lineage kinase-domain-like (MLKL). However, the regulation of necroptotic signaling pathway is far less investigated. Here we showed that c-Jun N-terminal kinases (JNK1 and JNK2) displayed kinase-dependent and -independent functions in regulating TNF- and TLRs-mediated necroptosis. We found that RIPK1 and RIPK3 promoted cell-death-independent JNK activation in macrophages, which contributed to pro-inflammatory cytokines production. Meanwhile, blocking the kinase activity of JNK dramatically reduced TNF and TLRs-induced necroptotic cell death. Consistently, inhibition of JNK activity protected mice from TNF-induced death and Staphylococcus aureus-mediated lung damage. However, depletion of JNK protein using siRNA sensitized macrophages to necroptosis that was triggered by LPS or poly I:C but still inhibited TNF-induced necroptosis. Mechanistic studies revealed that RIPK1 recruited JNK to the necrosome complex and their kinase activity was required for necrosome formation and the phosphorylation of MLKL in TNF- and TLRs-induced necroptosis. Loss of JNK protein consistently suppressed the phosphorylation of MLKL and necrosome formation in TNF-triggered necroptosis, but differentially promoted the phosphorylation of MLKL and necrosome formation in poly I:C-triggered necroptosis by promoting the oligomeration of TRIF. In conclusion, our findings define a differential role for JNK in regulating TNF- and TLRs-mediated necroptosis by their kinase or scaffolding activities.
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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.