ArticleThe Journal of biological chemistry2015
Apoptosis Signal-regulating Kinase 1 (ASK1)-p38 Pathway-dependent Cytoplasmic Translocation of the Orphan Nuclear Receptor NR4A2 Is Required for Oxidative Stress-induced Necrosis.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 52 citations in OpenAlex.
- Paeoniflorin as a candidate disease-modifying therapy for diabetic peripheral neuropathy: mechanisms, exposure challenges, and translational priorities.Frontiers in pharmacology · 2026Review
- SARS-CoV-2 spike triggers TLR7-dependent endolysosome dysfunction and senescence in human astrocytes.Journal of neuroinflammation · 2025Article
- The Organogermanium Compound 3-(trihydroxygermyl)propanoic Acid Exerts Anti-Inflammatory Effects via Adenosine-NR4A2 Signaling.International journal of molecular sciences · 2025Article
- Oxidative stress in poultry production.Poultry science · 2024Review
- Potential effects of Resatorvid and alpha lipoic acid on gentamicin-induced nephrotoxicity in rats.Pharmacology research & perspectives · 2024Article
- Mitogen-Activated Protein Kinase and Exploratory Nuclear Receptor Crosstalk in Cancer Immunotherapy.International journal of molecular sciences · 2023Review
- Endoplasmic Reticulum Stress Causing Apoptosis in a Mouse Model of an Ischemic Spinal Cord Injury.International journal of molecular sciences · 2023Article
- A Comprehensive Analysis and Anti-Cancer Activities of Quercetin in ROS-Mediated Cancer and Cancer Stem Cells.International journal of molecular sciences · 2022Review
- Deletion of p38γ attenuates ethanol consumption- and acetaminophen-induced liver injury in mice through promoting Dlg1.Acta pharmacologica Sinica · 2022Article
- NAMPT-dependent NADCell death discovery · 2022Article
- Thioredoxin-1 Rescues MPPMolecular neurobiology · 2021Article
- ASK1 inhibition reduces cell death and hepatic fibrosis in an Nlrp3 mutant liver injury model.JCI insight · 2020Article
- Functions of p38 MAP Kinases in the Central Nervous System.Frontiers in molecular neuroscience · 2020Review
- Article
- Organogermanium suppresses cell death due to oxidative stress in normal human dermal fibroblasts.Scientific reports · 2019Article
- The Thioredoxin System is Regulated by the ASK-1/JNK/p38/Survivin Pathway During Germ Cell Apoptosis.Molecules (Basel, Switzerland) · 2019Article
- Antimicrobial Peptide TP4 Induces ROS-Mediated Necrosis by Triggering Mitochondrial Dysfunction in Wild-Type and MutantCancers · 2019Article
- The Antioxidative Action of ZTP by Increasing Nrf2/ARE Signal Pathway.Evidence-based complementary and alternative medicine : eCAM · 2019Article
- Apoptosis signal regulating kinase-1 and NADPH oxidase mediate human amylin evoked redox stress and apoptosis in pancreatic beta-cells.Biochimica et biophysica acta. Biomembranes · 2018Article
- Co-sequencing and novel delayed anti-correlation identify function for pancreatic enriched microRNA biomarkers in a rat model of acute pancreatic injury.BMC genomics · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
p38 mitogen-activated protein kinases (MAPKs) play important roles in various cellular stress responses, including cell death, which is roughly categorized into apoptosis and necrosis. Although p38 signaling has been extensively studied, the molecular mechanisms of p38-mediated cell death are unclear. ASK1 is a stress-responsive MAP3K that acts as an upstream kinase of p38 and is activated by various stresses, such as oxidative stress. Here, we show that NR4A2, a member of the NR4A nuclear receptor family, acts as a necrosis promoter downstream of ASK1-p38 pathway during oxidative stress. Although NR4A2 is well known as a nucleus-localized transcription factor, we found that it is translocated into the cytosol after phosphorylation by p38. Because the phosphorylation site mutants of NR4A2 cannot rescue the cell death-promoting activity, ASK1-p38 pathway-dependent phosphorylation and subsequent cytoplasmic translocation of NR4A2 may be required for oxidative stress-induced cell death. In addition, NR4A2-mediated cell death does not depend on caspases and receptor-interacting protein 1 (RIP1)-RIP3 complex, suggesting that NR4A2 promotes an RIP kinase-independent necrotic type of cell death. Our findings may enable a more precise understanding of molecular mechanisms that regulate oxidative stress-induced and p38-mediated necrosis.
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