ArticleThe Journal of experimental medicine2003
Orphan nuclear receptor Nur77 is involved in caspase-independent macrophage cell death.
Article in The Journal of experimental medicine, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 87 citations in OpenAlex.
- SENP1: A perspective from immune cells to disease (Review).Oncology reports · 2025Review
- Chronic Stress-Induced and Tumor Derived SP1Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Nur77 protects the bladder urothelium from intracellular bacterial infection.Nature communications · 2024Article
- Caspase 6/NR4A1/SOX9 signaling axis regulates hepatic inflammation and pyroptosis in ischemia-stressed fatty liver.Cell death discovery · 2023Article
- Cellular Uptake of Silica and Gold Nanoparticles Induces Early Activation of Nuclear Receptor NR4A1.Nanomaterials (Basel, Switzerland) · 2022Article
- Autophagy Is Involved in Mesenchymal Stem Cell Death in Coculture with Chondrocytes.Cartilage · 2021Article
- Profound downregulation of neural transcription factor Npas4 and Nr4a family in fetal mice neurons infected with Zika virus.PLoS neglected tropical diseases · 2021Article
- TLR4 Cross-Talk With NLRP3 Inflammasome and Complement Signaling Pathways in Alzheimer's Disease.Frontiers in immunology · 2020Review
- Key Functions and Therapeutic Prospects of Nur77 in Inflammation Related Lung DiseasesThe American journal of pathology · 2019Review
- SUMO-triggered ubiquitination of NR4A1 controls macrophage cell death.Cell death and differentiation · 2017Article
- Matrine induces RIP3-dependent necroptosis in cholangiocarcinoma cells.Cell death discovery · 2017Article
- Substance P Receptor Signaling Mediates Doxorubicin-Induced Cardiomyocyte Apoptosis and Triple-Negative Breast Cancer Chemoresistance.BioMed research international · 2016Article
- Apoptosis Signal-regulating Kinase 1 (ASK1)-p38 Pathway-dependent Cytoplasmic Translocation of the Orphan Nuclear Receptor NR4A2 Is Required for Oxidative Stress-induced Necrosis.The Journal of biological chemistry · 2015Article
- NR4A1 is associated with chronic low-grade inflammation in patients with type 2 diabetes.Experimental and therapeutic medicine · 2014Article
- The Nuclear Orphan Receptor NR4A1 is Involved in the Apoptotic Pathway Induced by LPS and Simvastatin in RAW 264.7 Macrophages.Immune network · 2014Article
- Article
- Limited role of nuclear receptor Nur77 in Escherichia coli-induced peritonitis.Infection and immunity · 2014Article
- Article
- Nuclear receptors Nur77 and Nurr1 modulate mesenchymal stromal cell migration.Stem cells and development · 2012Article
- The nuclear receptor NR4A1 induces a form of cell death dependent on autophagy in mammalian cells.PloS one · 2012Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Activation-induced cell death in macrophages has been observed, but the mechanism remains largely unknown. Activation-induced cell death in macrophages can be independent from caspases, and the death of activated macrophages can even be triggered by the pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (zVAD). Here, we show that this type of macrophage death can occur in the septic mouse model and that toll-like receptor (TLR)-2 or TLR4 signaling is required in this process. We conclude that Nur77 is involved in the macrophage death because Nur77 expression correlates with cell death, and cell death is reduced significantly in Nur77-deficient macrophages. The extracellular signal-regulated kinase pathway, which is downstream of TLR2 or TLR4, and myocyte-specific enhancer binding factor 2 (MEF2) transcription factor activity, which is up-regulated by zVAD, are required for Nur77 induction and macrophage death. Reporter gene analysis suggests that Nap, Ets, Rce, and Sp1 sites in the Nur77 promoter are regulated by TLR4 signaling and that MEF2 sites in the Nur77 promoter are regulated by zVAD treatment. MEF2 transcription factors are constitutively expressed and degraded in macrophages, and zVAD increases MEF2 transcription factor activity by preventing the proteolytic cleavage and degradation of MEF2 proteins. This paper delineates the dual signaling pathways that are required for Nur77 induction in macrophages and demonstrates a role of Nur77 in caspase-independent cell death.
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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.