Affinage

Showing NR4A1 — NUR77 is a alias.

NR4A1

Nuclear receptor subfamily 4immunitygroup A member 1 · UniProt P22736

Length
598 aa
Mass
64.5 kDa
Annotated
2026-06-10
100 papers in source corpus 49 papers cited in narrative 49 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NR4A1 (Nur77/NGFIB/TR3) is an immediate-early orphan nuclear receptor and transcription factor whose biological output is dictated by subcellular localization, post-translational modification, and an unusually wide repertoire of protein and RNA interactions spanning transcriptional control, apoptosis, immune restraint, and metabolic regulation (PMID:16892086, PMID:34624217, PMID:29343483). In the nucleus it binds NGFIB response elements to directly activate steroidogenic and metabolic targets including CYP11B2 and HSD3B2 in adrenal cells (PMID:14645496, PMID:15208301), the Cebpa enhancer in hematopoietic stem cells (PMID:29343483), and SOD1 in endothelium (PMID:38290383), while also acting as a repressor: it occupies immediate-early gene bodies to inhibit RNA Pol II elongation and generate R-loops, restraining FOS and preventing chromosomal instability (PMID:34624217), and recruits the corepressor CoREST to suppress Runx3 during CD8 T cell development (PMID:25762306). A central function is restraint of inflammation—NR4A1 directly associates with NF-κB p65 to block κB-element binding and suppress cytokine production (PMID:25822914, PMID:15466594), and its loss drives M1 macrophage polarization and a pro-inflammatory TCA-cycle metabolic switch (PMID:22194622, PMID:30134173). Its transcriptional activity is gated by phosphorylation (Akt at Ser-350 within the DNA-binding domain reduces DNA binding and promotes 14-3-3 association (PMID:11274386, PMID:11438550); Mst1 at Thr-366 enhances activity (PMID:36623453); LPS-activated p38α counteracts NF-κB suppression (PMID:25822914)), by SUMO2/3 modification that recruits RNF4 for ubiquitin-dependent degradation (PMID:28622293), and by corepressors FHL2 and glycerol kinase that bind distinct domains (PMID:22049082, PMID:30821173). Beyond the nucleus, NR4A1 translocates to mitochondria where it converts Bcl-2 into a pro-apoptotic form to trigger cytochrome c release (PMID:16892086), sequesters LKB1 to attenuate AMPK activation (PMID:22983157), and acts as a cytoplasmic, m6A-dependent RNA-binding protein in P-bodies that destabilizes Tnf mRNA (PMID:37486903). Through these activities NR4A1 governs T cell tolerance and clonal deletion (PMID:30814730, PMID:8643610, PMID:22345564), β-cell and adipocyte proliferative fate (PMID:27221116, PMID:24706823, PMID:30277475), and mitochondrial/oxidative metabolism in muscle, vasculature, and heart (PMID:23028113, PMID:31993850, PMID:38834564).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1993 High

    Established that NR4A1 transcriptional output is directly gated by phosphorylation within its DNA-binding domain, the first mechanism explaining signal-dependent control of this immediate-early factor.

    Evidence In vitro PKA phosphorylation of purified DBD with Ser-340/Ser-350 mutagenesis and EMSA

    PMID:8227042

    Open questions at the time
    • Did not identify the physiological kinase in cells
    • Did not connect DNA-binding loss to a cellular phenotype
  2. 1996 High

    Defined a transcriptional apoptotic route by showing NR4A1 drives thymocyte death via FasL upregulation, placing it in negative selection.

    Evidence Transgenic nur77 overexpression with genetic epistasis in gld/gld FasL-defective mice

    PMID:8643610

    Open questions at the time
    • Did not address the later-discovered transcription-independent mitochondrial pathway
    • FasL induction mechanism not resolved at promoter level
  3. 1997 High

    Showed NR4A1 transcription is antagonized by the glucocorticoid receptor at the NurRE, integrating it into endocrine negative feedback.

    Evidence Luciferase reporters, in vitro binding, and GR mutant analysis in endocrine and T cell systems

    PMID:9315653

    Open questions at the time
    • Mechanism inferred by analogy to GR–AP-1 antagonism rather than fully resolved
    • Direct GR–Nur77 contact not structurally defined
  4. 2001 High

    Identified Akt as a survival-signaling kinase that phosphorylates Ser-350, suppressing DNA binding, promoting 14-3-3 association, and blocking NR4A1-induced apoptosis.

    Evidence Co-IP, in vitro/in vivo kinase assays, DNA-binding assays, and apoptosis rescue in T cells and fibroblasts (two independent studies)

    PMID:11274386 PMID:11438550

    Open questions at the time
    • Did not establish whether 14-3-3 binding governs cytoplasmic retention
    • Upstream stimuli setting Akt-Nur77 balance not mapped
  5. 2003 High

    Resolved NR4A1 as a direct transcriptional activator of steroidogenic genes, linking ACTH/angiotensin signaling to adrenal CYP11B2 and HSD3B2 expression.

    Evidence EMSA, promoter mutagenesis, and adenoviral overexpression in adrenocortical cells

    PMID:14645496 PMID:15208301

    Open questions at the time
    • Coactivator requirements at these promoters not defined
    • Did not address regulation by NR4A1 post-translational state
  6. 2003 High

    Connected innate immune signaling to NR4A1 induction and identified a caspase-independent macrophage death program downstream of TLR/ERK/MEF2.

    Evidence Nur77-deficient macrophages, promoter element mutagenesis, ERK inhibition, and septic mouse model

    PMID:12782711

    Open questions at the time
    • Effector mechanism of caspase-independent death unresolved
    • Did not separate transcriptional from mitochondrial Nur77 contributions
  7. 2006 High

    Consolidated the transcription-independent apoptotic mechanism in which mitochondrial NR4A1 converts Bcl-2 to a pro-apoptotic conformation triggering cytochrome c release.

    Evidence Review of subcellular fractionation, Nur77–Bcl-2 Co-IP, cytochrome c assays, and DBD-deletion constructs

    PMID:16892086

    Open questions at the time
    • Signals controlling nuclear-to-mitochondrial export not fully defined
    • Structural basis of the Bcl-2 conformational switch not resolved
  8. 2012 High

    Revealed a non-genomic cytoplasmic function: NR4A1 sequesters LKB1 to restrain AMPK, providing a druggable node in metabolic disease.

    Evidence Reciprocal Co-IP, subcellular fractionation, AMPK phosphorylation assay, Nur77-KO diabetic mice, and the TMPA probe with defined binding sites

    PMID:22983157

    Open questions at the time
    • Did not define the trigger for LKB1 release in vivo
    • Relationship to nuclear transcriptional role unclear
  9. 2012 High

    Mapped NR4A1's role in T cell fate decisions, including Bim-dependent clonal deletion and induction of Treg and metabolic gene programs after TCR signaling.

    Evidence Nr4a1-KO and TCR-transgenic mice with transcriptional profiling and apoptosis assays

    PMID:22345564

    Open questions at the time
    • Direct vs indirect control of Bim not resolved
    • Metabolic gene induction mechanism not dissected
  10. 2015 High

    Established direct anti-inflammatory restraint of NF-κB via NR4A1–p65 binding, and that p38α phosphorylation neutralizes this suppression—defining a pharmacological strategy.

    Evidence Reciprocal Co-IP, κB reporter assays, Nur77-biased compound screen, and LPS sepsis model

    PMID:25822914

    Open questions at the time
    • p38α phosphosite on Nur77 not identified here
    • Genome-wide breadth of NF-κB locus occupancy not addressed
  11. 2015 High

    Defined a corepressor mechanism in CD8 T cell development by which NR4A1 recruits CoREST to directly silence Runx3.

    Evidence Nr4a1-KO mice, flow cytometry, and ChIP at the Runx3 locus

    PMID:25762306

    Open questions at the time
    • CoREST recruitment determinants on NR4A1 not mapped
    • Generality of CoREST partnership at other loci unknown
  12. 2017 High

    Defined the degradative arm of NR4A1 regulation: SUMO2/3 modification recruits the SUMO-targeted E3 ligase RNF4 for ubiquitin-dependent turnover, controlling NF-κB output and macrophage death.

    Evidence SUMO/ubiquitin Co-IP, SUMO-site mutagenesis, PIAS3/RNF4/SENP1 perturbation, and functional macrophage assays

    PMID:28622293

    Open questions at the time
    • Did not resolve which functional pool is preferentially degraded
    • Signals triggering SUMOylation not defined
  13. 2018 High

    Showed NR4A1 enforces an anti-inflammatory macrophage metabolic state, with loss causing failure to downregulate IDH and succinate accumulation driving cytokine production.

    Evidence Nr4a1-KO macrophages with metabolomics, respiration assays, SDH inhibition, and atherosclerosis model

    PMID:22194622 PMID:30134173

    Open questions at the time
    • Direct transcriptional targets among metabolic enzymes not fully mapped
    • Link to mitochondrial Nur77 pool not established
  14. 2018 High

    Established direct enhancer occupancy controlling stem and progenitor proliferation, including NR4A1/NR4A3 binding the Cebpa enhancer in HSCs and antagonism of NF-κB inflammatory loci.

    Evidence Conditional Nr4a1/Nr4a3 double-KO mice with ChIP and HSC transcriptome profiling

    PMID:29343483

    Open questions at the time
    • Functional redundancy of NR4A1 vs NR4A3 at each locus not separated
    • Coregulator complement at the Cebpa enhancer unknown
  15. 2021 High

    Uncovered a chromatin function in which NR4A1 occupies IEG bodies to inhibit Pol II elongation, generate R-loops, and protect genome stability by restraining FOS.

    Evidence ChIP-seq, ATAC-seq, R-loop detection, and KO/OE in breast cancer cells with chromosomal instability assays

    PMID:34624217

    Open questions at the time
    • How replication stress triggers NR4A1 dissociation mechanistically unresolved
    • Relationship to its NBRE-based activation role not integrated
  16. 2023 High

    Identified an activating phosphorylation, Mst1 at Thr-366, that enhances NR4A1 transcriptional activity, contrasting the inhibitory Akt/PKA sites.

    Evidence In vitro kinase assay, LC-MS/MS site mapping, phospho-specific antibody, and in vivo embryo implantation model

    PMID:36623453

    Open questions at the time
    • Structural effect of T366 phosphorylation on the receptor not defined
    • Cross-talk with inhibitory phosphosites not examined
  17. 2023 High

    Defined a cytoplasmic, m6A-dependent RNA-binding function in which NR4A1 destabilizes Tnf mRNA in P-body microglia, extending its anti-inflammatory role to post-transcriptional control.

    Evidence RNA immunoprecipitation, P-body imaging, mRNA stability assays, and conditional microglial KO in a stroke model

    PMID:37486903

    Open questions at the time
    • RNA-binding interface on NR4A1 not structurally defined
    • Breadth of NR4A1-bound transcripts beyond Tnf unknown
  18. 2024 Medium

    Extended NR4A1's transcriptional reach into neuronal circuit wiring, showing cell-type-specific programs in PV and SST interneurons that shape axonal connectivity.

    Evidence Cell-type-specific conditional Nr4a1 KO with transcriptome profiling and connectivity/behavioral assays

    PMID:38754414

    Open questions at the time
    • Direct vs indirect targets among adhesion/repulsion genes not separated
    • Mechanism of opposite directionality between interneuron types unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NR4A1's distinct functional pools—NBRE-driven activator, IEG-body elongation repressor, mitochondrial Bcl-2 converter, LKB1 sequestrant, and P-body RNA destabilizer—are coordinately partitioned by ligand binding and post-translational state remains unresolved.
  • No unified model linking phosphorylation/SUMOylation code to localization choice
  • Endogenous physiological ligand status of the LBD undefined despite multiple synthetic antagonists/agonists
  • Quantitative balance among competing functions in a single cell unmeasured

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 6 GO:0140110 transcription regulator activity 6 GO:0098772 molecular function regulator activity 4 GO:0003723 RNA binding 3
Localization
GO:0005634 nucleus 5 GO:0005739 mitochondrion 4 GO:0005829 cytosol 2
Pathway
R-HSA-168256 Immune System 8 R-HSA-74160 Gene expression (Transcription) 6 R-HSA-162582 Signal Transduction 5 R-HSA-1430728 Metabolism 4 R-HSA-5357801 Programmed Cell Death 4
Partners
AKT1BCL2FHL2GLPKMAPK14RELASTK11STK4

Evidence

Reading pass · 49 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2019 NR4A1 is preferentially recruited to AP-1 binding sites in tolerant T cells, where it represses effector-gene expression by inhibiting AP-1 function. NR4A1 binding also promotes acetylation of histone 3 at lysine 27 (H3K27ac), leading to activation of tolerance-related genes. Genome-wide epigenetic profiling (ChIP-seq/ATAC-seq), gene expression analysis, NR4A1 overexpression and deletion in mouse T cell tolerance system Nature High 30814730
2001 Akt phosphorylates NR4A1 at Ser-350 within the DNA-binding domain, decreasing NR4A1 transcriptional activity by 50–85%. Akt physically interacts with NR4A1 as shown by co-immunoprecipitation, and this phosphorylation is phosphatidylinositol 3-kinase-dependent. Co-immunoprecipitation, in vitro and in vivo kinase assay, luciferase reporter assay, site-directed mutagenesis (Ser-350) Proceedings of the National Academy of Sciences of the United States of America High 11274386 11438550
2001 Akt inhibits NR4A1 DNA-binding activity and stimulates its association with 14-3-3 in a phosphorylation-dependent manner, thereby suppressing NR4A1-induced apoptosis in T cells and fibroblasts. DNA-binding assay, co-immunoprecipitation, overexpression in T cell hybridomas and fibroblasts, apoptosis assay The Journal of biological chemistry High 11438550
1993 Phosphorylation of Ser-350 (but not Ser-340) within the DNA-binding domain of NGFI-B/NR4A1 by protein kinase A or NGF-treated PC12 cell extracts reduces binding to the NGFI-B response element. Bacterial expression of purified DBD, in vitro phosphorylation by PKA, EMSA, site-directed mutagenesis (Ser-340, Ser-350 to Ala) The Journal of biological chemistry High 8227042
2012 NR4A1 (Nur77) binds and sequesters LKB1 in the nucleus, attenuating AMPK activation. A compound (TMPA) binds NR4A1 at specific sites, releases LKB1 to the cytoplasm, enabling LKB1 to phosphorylate AMPKα. Co-immunoprecipitation (Nur77–LKB1 interaction), subcellular fractionation, AMPK phosphorylation assay, Nur77 knockout diabetic mouse model, compound binding at specific Nur77 sites Nature chemical biology High 22983157
2015 NR4A1 directly associates with p65 (NF-κB) to block its binding to the κB element, suppressing inflammatory cytokine production. LPS-activated p38α phosphorylates NR4A1, counteracting this suppression; a compound blocking the Nur77–p38α interaction (targeting the NR4A1 ligand-binding domain) restores Nur77-mediated NF-κB inhibition. Co-immunoprecipitation (Nur77–p65, Nur77–p38α), luciferase reporter (κB element), compound screening from Nur77-biased library, LPS-induced sepsis mouse model Nature chemical biology High 25822914
1997 Glucocorticoid receptor (GR) antagonizes NR4A1 (Nur77)-dependent transcription by competing at the NurRE element of the POMC gene. GR repression partially blunts CRH-induced NUR77 mRNA and directly antagonizes Nur77 transcriptional activity; in vitro binding and GR mutation analysis indicate the mechanism is similar to GR–AP-1 antagonism. Transfection/luciferase reporter assays, in vitro binding experiments, GR mutant analysis, endocrine (CRH/POMC) and T cell systems Molecular and cellular biology High 9315653
2003 NR4A1 (NGFIB) and NURR1 bind two functional NGFIB response elements (NBRE-1 at -766/-759 and Ad5 at -129/-114) in the CYP11B2 (aldosterone synthase) promoter to activate its transcription; angiotensin II strongly induces both receptors, and calmodulin kinase partially mediates this induction. Transient transfection/reporter assays, sequential deletion and mutagenesis of CYP11B2 promoter, EMSA, adenoviral overexpression in H295R adrenocortical cells Molecular endocrinology (Baltimore, Md.) High 14645496
2004 NR4A1 (NGFIB) binds a consensus NGFIB response element in the HSD3B2 promoter to directly activate its transcription; adenoviral NGFIB overexpression increases cortisol production 8-fold and HSD3B2 mRNA 26-fold in human adrenal cells; ACTH rapidly induces NGFIB expression. Promoter deletion/mutagenesis, EMSA, adenoviral overexpression in primary and H295R adrenal cells, microarray, immunohistochemistry The Journal of biological chemistry High 15208301
1996 NR4A1 (Nur77/N10) overexpression in thymocytes induces apoptosis of CD4+CD8+ double-positive cells by upregulating Fas ligand (FasL), but not Fas receptor; apoptosis is largely blocked in a FasL-defective (gld/gld) background, establishing that one NR4A1 apoptotic pathway proceeds through FasL–Fas signaling. Transgenic mouse model (nur77/N10-Tg), genetic epistasis with gld/gld mice, flow cytometry of thymocyte populations, FasL expression analysis Proceedings of the National Academy of Sciences of the United States of America High 8643610
2006 NR4A1 (Nur77) migrates from the nucleus to the mitochondria where it binds Bcl-2 and conformationally converts it from a survival factor into a pro-apoptotic protein, triggering cytochrome c release. Reviewed/summarized from multiple experimental studies including subcellular fractionation, co-immunoprecipitation (Nur77–Bcl-2), cytochrome c release assays, mutant constructs lacking DNA-binding domain Oncogene High 16892086
2011 Absence of NR4A1 (Nur77) in macrophages increases TLR4 mRNA/protein expression and NF-κB p65 phosphorylation, polarizing macrophages toward a pro-inflammatory M1 phenotype; NF-κB inhibition blocks the excess activation of Nur77-deficient macrophages. Nur77−/− chimeric mice on Ldlr−/− background, Western blot (p65 phosphorylation, TLR4), NFκB inhibitor rescue, macrophage cytokine profiling Circulation research High 22194622
2018 NR4A1 functions as a key upstream transcriptional regulator of the pro-inflammatory metabolic switch in macrophages; Nur77-deficient macrophages fail to downregulate isocitrate dehydrogenase (IDH) expression and accumulate higher succinate and other TCA metabolites in an SDH-dependent manner, producing more nitric oxide and pro-inflammatory cytokines. Nr4a1−/− macrophages, metabolomic analysis, mitochondrial respiration assays, succinate dehydrogenase inhibitor rescue, in vivo atherosclerosis model Cell reports High 30134173
2017 NR4A1 is sumoylated by SUMO2/3 at two specific sites; poly-SUMO modification targets NR4A1 for polyubiquitination by the SUMO-dependent E3 ligase RNF4, leading to its degradation. PIAS3 promotes SUMOylation, SENP1 reverses it. Mutation of SUMO sites stabilizes NR4A1, and SUMOylation is required for proper control of NF-κB signaling and macrophage cell death. Co-immunoprecipitation (SUMO/ubiquitin assays), SUMO site mutagenesis, RNF4/PIAS3/SENP1 knockdown/overexpression, NF-κB reporter assay, macrophage cell death assay Cell death and differentiation High 28622293
2011 FHL2 is a co-repressor of NR4A1 (Nur77); each of the four LIM domains of FHL2 can bind Nur77 via Nur77's N-terminal and DNA-binding domains. FHL2 inhibits Nur77 association with target gene (enolase3) promoter DNA and represses Nur77 transcriptional activity in a dose-dependent manner. Yeast two-hybrid, co-immunoprecipitation, domain mapping by deletion mutants, ChIP (enolase3 promoter), shRNA-mediated FHL2 knockdown, reporter assays The Journal of biological chemistry High 22049082
2015 Nr4a1 recruits the corepressor CoREST to directly suppress Runx3 expression in CD8+ T cells, controlling CD8 T cell development; loss of Nr4a1 increases Runx3 expression and causes a 2-fold increase in CD8+ T cells in thymus and periphery. Nr4a1 KO mice, flow cytometry, ChIP (CoREST recruitment to Runx3 locus), gene expression analysis Scientific reports High 25762306
2021 NR4A1 localizes across the gene body and 3' UTR of immediate early genes (IEGs) and inhibits transcriptional elongation by RNA Pol II, generating R-loops and accessible chromatin domains. Acute replication stress causes NR4A1 dissociation and a burst of IEG expression. Deletion of NR4A1 causes chromosomal instability and proliferative failure driven by deregulated FOS expression. ChIP-seq (NR4A1 occupancy at IEG bodies), ATAC-seq, R-loop detection, NR4A1 deletion and overexpression in breast cancer cells, chromosomal instability assays Molecular cell High 34624217
2020 In the Hippo pathway, YAP regulates NR4A1 transcription, phosphorylation, and mitochondrial localization. NR4A1 in turn acts as a feedback inhibitor of YAP by promoting its degradation, forming a regulatory loop that coordinates cell proliferation and apoptosis during liver regeneration and tumorigenesis. YAP gain/loss of function, NR4A1 reporter assays, phosphorylation assays, mitochondrial fractionation, in vivo liver regeneration and tumor models Cell reports Medium 33086070
2012 Nr4a1 participates in the induction of Bim after TCR triggering, contributing to clonal deletion; Nr4a1 also positively controls several Treg signature transcripts (Ikzf2, Tnfrsf9) and induces a coordinated set of glycolytic and Krebs cycle enzymes in response to TCR signals, thereby influencing T cell fate determination. Nr4a1 KO mice, TCR transgenic models, transcriptional profiling of Nr4a1KO thymocytes under selection, apoptosis assays, Bim induction assays Proceedings of the National Academy of Sciences of the United States of America High 22345564
2010 β-catenin activates NR4A1 (Nur77) expression through AP-1 (c-Fos/c-Jun) binding and transactivation of the Nur77 promoter; elevated Nur77 in colon cancer cells upregulates antiapoptotic BRE and angiogenic VEGF, enhancing growth and migration. Promoter reporter and mutagenesis assays, ChIP (AP-1 at Nur77 promoter), β-catenin siRNA/overexpression, colon cancer cell functional assays FASEB journal Medium 20847229
2003 NR4A1 (Nur77) is involved in caspase-independent macrophage cell death; its induction requires TLR2/TLR4 signaling through the ERK pathway and MEF2 transcription factor activity. Reporter gene analysis identifies Nap, Ets, Rce, Sp1, and MEF2 elements in the Nur77 promoter as regulated by these signals. Nur77-deficient macrophages (genetic KO), reporter gene analysis (Nur77 promoter elements), septic mouse model, ERK inhibitor studies, zVAD-induced MEF2 activation The Journal of experimental medicine High 12782711
2014 NR4A1 (Nur77) regulates ROS and endoplasmic reticulum stress in pancreatic cancer cells via transcriptional regulation of TXNDC5; NR4A1 knockdown decreases TXNDC5 expression, elevating ROS, and activating ER stress/proapoptotic pathways. DIM-C-pPhOH binds NR4A1 and acts as an antagonist. RNAi knockdown, NR4A1 antagonist (DIM-C-pPhOH) treatment, proteomic analysis, ROS assay, antioxidant rescue, gene expression profiling Molecular cancer research : MCR Medium 24515801
2014 C-DIM compounds (including DIM-C-pPhOH) directly bind the ligand-binding domain of NR4A1 with high affinity and act as NR4A1 antagonists in colon cancer cells, inhibiting NR4A1-dependent transactivation, decreasing survivin and Sp-regulated gene expression, and inhibiting mTOR signaling. Direct LBD binding assays, molecular modeling of NR4A1 LBD, luciferase reporter (NR4A1-responsive), RNAi, cell proliferation and apoptosis assays Molecular endocrinology (Baltimore, Md.) Medium 25099012
2018 NR4A1 regulates β1-integrin gene expression to control basal migration of breast cancer cells (TGF-β-independent); NR4A1 nuclear export is an essential step in TGF-β-induced cell migration, and NR4A1 also controls β3-integrin expression. RNAi (siNR4A1), nuclear export inhibitor (leptomycin B), NR4A1 antagonists (DIM-C-pPhOH), migration assays, β1/β3-integrin expression analysis Molecular and cellular biology Medium 26929200
2018 TGF-β/TGFβR/PKA/MKK4-7/JNK signaling phosphorylates and induces nuclear export of NR4A1; cytoplasmic NR4A1 then forms a complex with Axin2, Arkadia (RNF111), and RNF12 (RLIM) to drive proteasomal degradation of SMAD7, thereby enhancing lung cancer cell migration. Nuclear export inhibitor (leptomycin B), JNK inhibitor (SP600125), NR4A1 antagonist, co-immunoprecipitation (NR4A1–Axin2/Arkadia/RNF12 complex), SMAD7 degradation assay, migration assays Molecular cancer research : MCR Medium 30072581
2018 NR4A1 controls CD8+ T cell development through direct transcriptional suppression of Runx3 by recruiting the corepressor CoREST (also reported in PMID 25762306). Separate finding: NR4A1 regulates macrophage polarization and restrains pro-inflammatory NF-κB signaling by directly opposing NFκB activation of IκB-α (inducing IκB-α) and suppressing IKK-β. shNur77 in RAW264.7 osteoclast model, siIκB-α and siIKK-β rescue experiments, NF-κB reporter, Nur77 KO mice Journal of cellular and molecular medicine Medium 35181992
2019 Glycerol kinase (Gyk isoform b) acts as a novel co-repressor of NR4A1 in the liver by binding the C-terminal ligand-binding domain of NR4A1 (not the N-terminal AF-1 domain); this protein–protein interaction inhibits NR4A1 transcriptional activity and suppresses expression of gluconeogenic target genes in vivo. Co-immunoprecipitation (Gyk–NR4A1), domain mapping, reporter assays, Gyk overexpression in vitro and in vivo (fasted and diabetic mice), gene expression analysis FASEB journal Medium 30821173
2020 NR4A1 (Nur77) directly binds and destabilizes Tnf mRNA in microglia in an N6-methyladenosine (m6A)-dependent manner, functioning as a cytoplasmic RNA-binding protein in processing bodies (P-bodies). Conditional microglial deletion of Nr4a1 elevates Tnf expression and worsens ischemic stroke outcomes. Subcellular localization (P-bodies by imaging), RNA immunoprecipitation (NR4A1–Tnf mRNA binding), mRNA stability assay, m6A-dependent mechanism, conditional microglial Nr4a1 KO, stroke mouse model PLoS biology High 37486903
2018 NR4A1 in vascular endothelial cells increases thrombomodulin mRNA stability (not promoter activity), whereas the related NR4A3 (Nor1) enhances thrombomodulin expression via induction of KLF2/4. Nur77 deficiency increases susceptibility to arterial thrombosis. Adenoviral NR4A1 overexpression in ECs and mouse liver, Nur77 KO mice, mRNA stability assay, promoter reporter assay, protein C activity assay, thrombosis model Arteriosclerosis, thrombosis, and vascular biology Medium 26634653
2024 Nur77 increases GCH1 mRNA stability by inhibiting microRNA-133a expression, and upregulates SOD1 by directly binding the SOD1 promoter in vascular endothelial cells, thereby activating NO production and anti-oxidant pathways that attenuate endothelial dysfunction. Nur77 KO and endothelial-specific Tg mice, vasodilatation assay, ROS measurement (DHE staining), miRNA-133a overexpression/inhibition, ChIP (Nur77 at SOD1 promoter), mRNA stability assay Redox biology Medium 38290383
2018 NR4A1 controls CD8+ T cell development; separately, NR4A1 promotes adipocyte progenitor (AP) quiescence — gain of function decreases adipogenesis while loss of function increases proliferative and adipogenic capacity; Nr4a1−/− AP transplantation into obese WT recipients improves glucose homeostasis. NR4A1 gain/loss-of-function in primary APs ex vivo, Nr4a1−/− mouse adipose tissue analysis, AP transplantation into obese recipients, ATAC-seq, transcriptomics The Journal of clinical investigation Medium 30277475
2018 NR4A1 and NR4A3 restrict HSC proliferation partly through direct binding to a hematopoietic-specific Cebpa enhancer, activating Cebpa transcription. NR4A1/3 also occupy regulatory regions of NF-κB-regulated inflammatory cytokines and antagonize NF-κB activation. Conditional Nr4a1/Nr4a3 double KO mice, ChIP (NR4A1/3 binding to Cebpa enhancer and NF-κB cytokine loci), transcriptome profiling of HSCs, flow cytometry, DNA damage assays Blood High 29343483
2012 Nur77 expression in skeletal muscle enhances mitochondrial function and oxidative metabolism; MCK-Nur77 transgenic mice show increased oxidative fiber abundance, elevated mitochondrial DNA content, increased complex I of the electron transport chain, and favor fatty acid oxidation over glucose oxidation. MCK-Nur77 transgenic mice, mitochondrial respiration assays, metabolomics, electron transport chain component analysis, muscle contractile function assay Journal of lipid research Medium 23028113
2016 β-cell deletion of Nr4a1 and Nr4a3 reduces mitochondrial respiration and glucose-stimulated insulin secretion, associated with decreased expression of mitochondrial dehydrogenase subunits Idh3g and Sdhb, and impaired ATP production. β-cell-specific Nr4a1/Nr4a3 KO, permeabilized cell respirometry, intact cell glucose-stimulated oxygen consumption, insulin secretion assay, ATP production assay, gene expression American journal of physiology. Endocrinology and metabolism Medium 27221116
2014 Nkx6.1 induces expression of Nr4a1 (and Nr4a3), and these receptors are both necessary and sufficient for Nkx6.1-mediated β-cell proliferation; Nr4a1 overexpression increases E2F1 and cyclin E1, and induces APC components including UBE2C, promoting degradation of the cell cycle inhibitor p21. Global Nr4a1 KO reduces β-cell area in neonatal mice. Adenoviral Nr4a1 overexpression in rat islets, Nr4a1 KO mice (β-cell area quantification), gene expression analysis, cell cycle marker assays Proceedings of the National Academy of Sciences of the United States of America Medium 24706823
2004 NR4A1 (Nur77) represses NF-κB-driven IL-2 promoter activation through its N-terminal AF-1 domain by inhibiting NF-κB components (p65 and c-Rel) binding at low-affinity κB sites in the IL-2 promoter; this repression is specific to low-affinity sites and not observed on high-affinity HIV LTR κB sites. Cotransfection/luciferase reporter assays (IL-2 promoter and mutants, CD28RE with NF-κB sites, HIV LTR), Nur77 domain mutants (AF-1 deletion), Jurkat T cells Nucleic acids research Medium 15466594
2020 NR4A1 (Nur77) directly binds WFDC21P promoter response elements to transcriptionally activate WFDC21P lncRNA expression in HCC; this suppresses glycolysis by NR4A1/WFDC21P-dependent disruption of PFKP and PKM2 function. ChIP (Nur77 binding WFDC21P promoter NBRE elements), reporter assays, KO/KD in vitro and in vivo tumor models, Csn-B agonist treatment Oncogene Medium 31959898
2023 Mst1 kinase phosphorylates NR4A1 at threonine 366 (T366), enhancing its transcriptional activity and increasing downstream β3-integrin expression in endometrial epithelial cells, thereby promoting trophoblast-uterine epithelium adhesion and embryo implantation. In vitro kinase assay (Mst1 phosphorylating Nur77), LC-MS/MS identification of T366, phos-tag SDS-PAGE, phospho-specific antibody (pT366), mouse embryo adhesion assay, delayed implantation mouse model, RNA-seq EBioMedicine High 36623453
2020 NR4A1 (Nr4a1) contributes to cocaine-induced neuroadaptation by directly controlling CARTPT expression; Nr4a1 deletion or CRISPR-based Nr4a1 activation demonstrates direct causality for sustained Cartpt transcription during cocaine abstinence, associated with depletion of H3K27me3 and enrichment of H3K27ac and H3K4me3 at the Cartpt locus. CRISPR-mediated Nr4a1 activation, small molecule Nr4a1 activation, ChIP (H3K27me3, H3K27ac, H3K4me3), cocaine behavioral assays Nature communications Medium 31980629
2016 NR4A1 regulates PAX3-FOXO1A expression in alveolar rhabdomyosarcoma through an NR4A1/Sp4 complex that binds GC-rich promoter regions; RNAi of NR4A1 or NR4A1 antagonists reduce PAX3-FOXO1A and its downstream effectors. RNAi (siNR4A1), NR4A1 antagonists (C-DIM), ChIP/promoter reporter (NR4A1/Sp4 at PAX3-FOXO1A promoter GC-rich elements), gene expression profiling, migration assays Cancer research Medium 27864345
2022 Resveratrol binds the ligand-binding domain of NR4A1 with KD = 2.4 µM (measured by isothermal titration calorimetry) and acts as an NR4A1 antagonist, inhibiting NR4A1-dependent transactivation in lung cancer cells. Isothermal titration calorimetry (direct binding to NR4A1 LBD), luciferase reporter (NR4A1-responsive), functional assays (proliferation, migration), gene expression Molecular pharmacology Medium 35680166
2020 NR4A1 promotes mitochondrial fission in VSMCs by activating DNA-PKcs and p53 and facilitating Drp1 migration to mitochondria; NR4A1 also inhibits BNIP3-related mitophagy, causing mitochondrial dysfunction and contributing to vascular calcification. NR4A1 siRNA knockdown, Western blot (Drp1, BNIP3, LC3-II, p62), mRFP-GFP-LC3 adenovirus, mPTP opening rate, membrane potential, TEM, ATP/OCR measurement, ex vivo calcification staining Apoptosis Medium 31993850
2018 NR4A1 regulates Parkin-mediated mitophagy in endothelial cells through post-transcriptional modification of Parkin via CaMKII; ox-LDL-induced NR4A1 activates CaMKII, which phosphorylates Parkin, driving excessive mitophagy and endothelial apoptosis. NR4A1 KO/overexpression in AECs, CaMKII inhibitor, Parkin phosphorylation assay, mitochondrial function assays, in vitro and high-fat diet mouse model Cell stress & chaperones Medium 29470798
2024 NR4A1 expression is regulated by the transcription factor Creb5 in the PI3K/AKT pathway in cardiomyocytes; semaglutide reduces NR4A1 expression and its translocation to mitochondria through the Creb5/NR4A1 axis, and NR4A1 knockdown ameliorates mitochondrial dysfunction and abnormal metabolic shifts in the heart. Transcriptional analysis (Creb5/NR4A1 axis), NR4A1 knockdown in cardiomyocytes, metabolomics, mitochondrial structure/function assays, mouse pressure-overload heart failure model Nature communications Medium 38834564
2023 Nr4a1 overexpression protects Sirt1 protein from proteasomal degradation through negative transcriptional regulation of the E3 ubiquitin ligase MDM2; Nr4a1 deletion shortens mouse lifespan and accelerates aging in multiple tissues. Nr4a1 KO mice (lifespan/aging phenotype), overexpression of Nr4a1 (MDM2 reporter assay, Sirt1 protein stability), proteasome inhibitor rescue, gene expression analysis Aging cell Medium 36883265
2021 MEF2D transcriptionally activates NR4A1 expression in response to amino acid deficiency; NR4A1 in turn activates FAM134B2 (RETREG1) expression to drive reticulophagy, contributing to amino acid homeostasis. Gene expression profiling, reporter assays, loss-of-function experiments in amino acid-deficient conditions Autophagy Low 34517786
2016 NR4A1 interacts with NR2B (NMDA receptor subunit) as shown by reciprocal co-immunoprecipitation in neurons; NR4A1 knockdown reduces surface NR2B expression by promoting NR2B internalization (reduced p-NR2B Tyr1472 and reduced NR2B in postsynaptic density), and alleviates seizure severity. Reciprocal co-immunoprecipitation (NR4A1–NR2B), lentiviral shNR4A1, postsynaptic density fractionation, seizure behavioral assay, pilocarpine mouse model Scientific reports Medium 27876882
2020 SUMOylation of NR4A1 is required for induction of autophagic cell death; triple mutation of SUMO sites reduces NR4A1 SUMOylation, increases transcriptional activity, alters intracellular distribution, and impairs autophagic cell death induction. SUMO site mutagenesis (triple mutant), SUMOylation assay, transcriptional reporter, subcellular localization imaging, autophagic cell death assay PloS one Medium 32210435
2024 Nr4a1 regulates contrasting transcriptional programs in parvalbumin- and somatostatin-positive GABAergic interneurons in the mouse forebrain, exerting cell-type-specific effects on local axonal wiring; loss of Nr4a1 causes bidirectional transcriptional switches in genes including surface adhesion and repulsion molecules. Conditional Nr4a1 KO in PV and SST interneurons, transcriptome profiling, synaptic connectivity assays, behavioral learning assays Neuron Medium 38754414

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 Genome-wide analysis identifies NR4A1 as a key mediator of T cell dysfunction. Nature 431 30814730
2011 NR4A1 (Nur77) deletion polarizes macrophages toward an inflammatory phenotype and increases atherosclerosis. Circulation research 377 22194622
2006 p53 and Nur77/TR3 - transcription factors that directly target mitochondria for cell death induction. Oncogene 212 16892086
2003 The orphan nuclear receptors NURR1 and NGFIB regulate adrenal aldosterone production. Molecular endocrinology (Baltimore, Md.) 164 14645496
1997 Antagonism between Nur77 and glucocorticoid receptor for control of transcription. Molecular and cellular biology 157 9315653
2001 Akt phosphorylates and regulates the orphan nuclear receptor Nur77. Proceedings of the National Academy of Sciences of the United States of America 156 11274386
2012 The orphan nuclear receptor Nur77 regulates LKB1 localization and activates AMPK. Nature chemical biology 155 22983157
2015 Impeding the interaction between Nur77 and p38 reduces LPS-induced inflammation. Nature chemical biology 146 25822914
2001 Akt inhibits the orphan nuclear receptor Nur77 and T-cell apoptosis. The Journal of biological chemistry 132 11438550
2018 Nuclear Receptor Nur77 Limits the Macrophage Inflammatory Response through Transcriptional Reprogramming of Mitochondrial Metabolism. Cell reports 116 30134173
1996 Apoptosis of nur77/N10-transgenic thymocytes involves the Fas/Fas ligand pathway. Proceedings of the National Academy of Sciences of the United States of America 115 8643610
2004 The orphan nuclear receptor NGFIB regulates transcription of 3beta-hydroxysteroid dehydrogenase. implications for the control of adrenal functional zonation. The Journal of biological chemistry 114 15208301
2012 Nuclear receptor Nr4a1 modulates both regulatory T-cell (Treg) differentiation and clonal deletion. Proceedings of the National Academy of Sciences of the United States of America 108 22345564
2007 Targeting Nur77 translocation. Expert opinion on therapeutic targets 104 17150035
2020 Lactate accelerates vascular calcification through NR4A1-regulated mitochondrial fission and BNIP3-related mitophagy. Apoptosis : an international journal on programmed cell death 101 31993850
2010 Regulation of Nur77 expression by β-catenin and its mitogenic effect in colon cancer cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 101 20847229
2014 The orphan nuclear receptor NR4A1 (Nur77) regulates oxidative and endoplasmic reticulum stress in pancreatic cancer cells. Molecular cancer research : MCR 97 24515801
2014 Diindolylmethane analogs bind NR4A1 and are NR4A1 antagonists in colon cancer cells. Molecular endocrinology (Baltimore, Md.) 94 25099012
2020 A Regulation Loop between YAP and NR4A1 Balances Cell Proliferation and Apoptosis. Cell reports 90 33086070
2011 Targeting NR4A1 (TR3) in cancer cells and tumors. Expert opinion on therapeutic targets 87 21204731
1993 The phosphorylation and DNA binding of the DNA-binding domain of the orphan nuclear receptor NGFI-B. The Journal of biological chemistry 87 8227042
2014 Nkx6.1 regulates islet β-cell proliferation via Nr4a1 and Nr4a3 nuclear receptors. Proceedings of the National Academy of Sciences of the United States of America 85 24706823
2006 Nur77 and retinoid X receptors: crucial factors in dopamine-related neuroadaptation. Trends in neurosciences 83 17134767
2024 Semaglutide ameliorates cardiac remodeling in male mice by optimizing energy substrate utilization through the Creb5/NR4a1 axis. Nature communications 78 38834564
2005 Barrier function at HMR. Molecular cell 74 16137626
2012 Skeletal muscle Nur77 expression enhances oxidative metabolism and substrate utilization. Journal of lipid research 73 23028113
2004 Nur77 family of nuclear hormone receptors. Current drug targets. Inflammation and allergy 72 15584889
2003 Orphan nuclear receptor Nur77 is involved in caspase-independent macrophage cell death. The Journal of experimental medicine 72 12782711
2020 Nr4a1 suppresses cocaine-induced behavior via epigenetic regulation of homeostatic target genes. Nature communications 71 31980629
2018 Characteristics of Nur77 and its ligands as potential anticancer compounds (Review). Molecular medicine reports 70 30272297
2020 Nur77-activated lncRNA WFDC21P attenuates hepatocarcinogenesis via modulating glycolysis. Oncogene 66 31959898
2016 NR4A1 Antagonists Inhibit β1-Integrin-Dependent Breast Cancer Cell Migration. Molecular and cellular biology 65 26929200
2004 Negative cross-talk between the human orphan nuclear receptor Nur77/NAK-1/TR3 and nuclear factor-kappaB. Nucleic acids research 60 15466594
2021 Nuclear receptor Nur77: its role in chronic inflammatory diseases. Essays in biochemistry 59 34328179
2008 Modulation of orphan nuclear receptor Nur77-mediated apoptotic pathway by acetylshikonin and analogues. Cancer research 59 18974131
2021 NR4A1 regulates expression of immediate early genes, suppressing replication stress in cancer. Molecular cell 58 34624217
2015 The nuclear orphan receptor NR4A1 and NR4A3 as tumor suppressors in hematologic neoplasms. Current drug targets 58 25410408
2018 NR4A1 and NR4A3 restrict HSC proliferation via reciprocal regulation of C/EBPα and inflammatory signaling. Blood 57 29343483
2015 Nuclear Receptor 4A1 (NR4A1) as a Drug Target for Renal Cell Adenocarcinoma. PloS one 57 26035713
2012 Nur77: a potential therapeutic target in cancer. Expert opinion on therapeutic targets 53 22537097
2011 Nuclear receptors Nur77 and Nurr1 modulate mesenchymal stromal cell migration. Stem cells and development 53 21480782
2018 NR4A1 contributes to high-fat associated endothelial dysfunction by promoting CaMKII-Parkin-mitophagy pathways. Cell stress & chaperones 52 29470798
2017 SUMO-triggered ubiquitination of NR4A1 controls macrophage cell death. Cell death and differentiation 47 28622293
2014 Non-genomic effects of the NR4A1/Nur77/TR3/NGFIB orphan nuclear receptor. Steroids 46 25555471
2021 Nr4A1 modulates inflammation-associated intestinal fibrosis and dampens fibrogenic signaling in myofibroblasts. American journal of physiology. Gastrointestinal and liver physiology 45 34288735
2018 NR4A1 is Involved in Fibrogenesis in Ovarian Endometriosis. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 45 29669342
2018 Key Functions and Therapeutic Prospects of Nur77 in Inflammation Related Lung Diseases. The American journal of pathology 45 30414411
2016 β-Cell deletion of Nr4a1 and Nr4a3 nuclear receptors impedes mitochondrial respiration and insulin secretion. American journal of physiology. Endocrinology and metabolism 45 27221116
2011 FHL2 protein is a novel co-repressor of nuclear receptor Nur77. The Journal of biological chemistry 42 22049082
2004 A role for the NGFI-B family in adrenal zonation and adrenocortical disease. Endocrine research 41 15666793
2006 Nur77 gene knockout alters dopamine neuron biochemical activity and dopamine turnover. Biological psychiatry 40 16893530
2022 Therapeutic potential of NR4A1 in cancer: Focus on metabolism. Frontiers in oncology 36 36052242
2020 NR4A1 Deletion in Marginal Zone B Cells Exacerbates Atherosclerosis in Mice-Brief Report. Arteriosclerosis, thrombosis, and vascular biology 36 32907369
2017 Tonic LAT-HDAC7 Signals Sustain Nur77 and Irf4 Expression to Tune Naive CD4 T Cells. Cell reports 34 28538176
2003 Regulation of NGFI-B expression during the ovulatory process. Molecular and cellular endocrinology 34 12770726
2015 The nuclear receptor nr4a1 controls CD8 T cell development through transcriptional suppression of runx3. Scientific reports 33 25762306
2023 Noncanonical contribution of microglial transcription factor NR4A1 to post-stroke recovery through TNF mRNA destabilization. PLoS biology 32 37486903
2021 Orphan nuclear receptor 4A1 (NR4A1) and novel ligands. Essays in biochemistry 32 34096590
2016 PAX3-FOXO1A Expression in Rhabdomyosarcoma Is Driven by the Targetable Nuclear Receptor NR4A1. Cancer research 31 27864345
2018 TGFβ-Induced Lung Cancer Cell Migration Is NR4A1-Dependent. Molecular cancer research : MCR 30 30072581
2018 Targeting nuclear receptor NR4A1-dependent adipocyte progenitor quiescence promotes metabolic adaptation to obesity. The Journal of clinical investigation 30 30277475
2023 Nr4a1 promotes renal interstitial fibrosis by regulating the p38 MAPK phosphorylation. Molecular medicine (Cambridge, Mass.) 29 37161357
2023 Oxidative stress impairs the Nur77-Sirt1 axis resulting in a decline in organism homeostasis during aging. Aging cell 28 36883265
2022 Nur77 Prevents Osteoporosis by Inhibiting the NF-κB Signalling Pathway and Osteoclast Differentiation. Journal of cellular and molecular medicine 28 35181992
2023 Flavonoids Quercetin and Kaempferol Are NR4A1 Antagonists and Suppress Endometriosis in Female Mice. Endocrinology 27 37652054
2021 NR4A1 Ligands as Potent Inhibitors of Breast Cancer Cell and Tumor Growth. Cancers 26 34072371
2019 Glycerol kinase interacts with nuclear receptor NR4A1 and regulates glucose metabolism in the liver. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 26 30821173
2018 Nuclear Receptor Nur77 Deficiency Alters Dendritic Cell Function. Frontiers in immunology 26 30123220
2016 NR4A1 Knockdown Suppresses Seizure Activity by Regulating Surface Expression of NR2B. Scientific reports 26 27876882
2024 Nur77 improves ovarian function in reproductive aging mice by activating mitophagy and inhibiting apoptosis. Reproductive biology and endocrinology : RB&E 25 39044215
2022 mPGES-2 blockade antagonizes β-cell senescence to ameliorate diabetes by acting on NR4A1. Nature metabolism 25 35228744
2022 hUMSCs Transplantation Regulates AMPK/NR4A1 Signaling Axis to Inhibit Ovarian Fibrosis in POI Rats. Stem cell reviews and reports 25 36307672
2020 Bis-Indole-Derived Nuclear Receptor 4A1 (NR4A1, Nur77) Ligands as Inhibitors of Endometriosis. Endocrinology 25 32099996
2015 Antithrombotic Effects of Nur77 and Nor1 Are Mediated Through Upregulating Thrombomodulin Expression in Endothelial Cells. Arteriosclerosis, thrombosis, and vascular biology 25 26634653
2007 Nuclear orphan receptor TR3/Nur77 mediates melanoma cell apoptosis. Cancer biology & therapy 25 17297306
2024 Nur77 mitigates endothelial dysfunction through activation of both nitric oxide production and anti-oxidant pathways. Redox biology 24 38290383
2022 RESVERATROL BINDS NUCLEAR RECEPTOR 4A1 (NR4A1) AND ACTS AS AN NR4A1 ANTAGONIST IN LUNG CANCER CELLS. Molecular pharmacology 24 35680166
2015 Pgc-1α and Nr4a1 Are Target Genes of Circadian Melatonin and Dopamine Release in Murine Retina. Investigative ophthalmology & visual science 24 26393668
2021 MEF2D-NR4A1-FAM134B2-mediated reticulophagy contributes to amino acid homeostasis. Autophagy 23 34517786
2019 MiR-506 Suppresses Colorectal Cancer Development by Inhibiting Orphan Nuclear Receptor NR4A1 Expression. Journal of Cancer 23 31293661
2018 NR4A1 retards adipocyte differentiation or maturation via enhancing GATA2 and p53 expression. Journal of cellular and molecular medicine 23 30044048
2023 Mst1-mediated phosphorylation of Nur77 improves the endometrial receptivity in human and mice. EBioMedicine 22 36623453
2021 Nuclear Receptor Nur77 Controls Cardiac Fibrosis through Distinct Actions on Fibroblasts and Cardiomyocytes. International journal of molecular sciences 22 33562500
2018 Bis-Indole-Derived NR4A1 Ligands and Metformin Exhibit NR4A1-Dependent Glucose Metabolism and Uptake in C2C12 Cells. Endocrinology 22 29635345
2016 Regulation of Nuclear Receptor Nur77 by miR-124. PloS one 22 26840408
2019 Nuclear receptor 4A1 (NR4A1) antagonists induce ROS-dependent inhibition of mTOR signaling in endometrial cancer. Gynecologic oncology 21 31053403
2019 Inhibition of NR4A1 Promotes ROS Accumulation and IL24-Dependent Growth Arrest in Rhabdomyosarcoma. Molecular cancer research : MCR 21 31462501
2015 Calcium-dependent Nr4a1 expression in mouse Leydig cells requires distinct AP1/CRE and MEF2 elements. Journal of molecular endocrinology 21 26647388
2024 PROTAC-mediated NR4A1 degradation as a novel strategy for cancer immunotherapy. The Journal of experimental medicine 20 38334978
2021 Negative feedback by NUR77/Nr4a1 restrains B cell clonal dominance during early T-dependent immune responses. Cell reports 20 34469720
2023 GLP-2 Improves Hepatic Inflammation and Fibrosis in Mdr2-/- Mice Via Activation of NR4a1/Nur77 in Hepatic Stellate Cells and Intestinal FXR Signaling. Cellular and molecular gastroenterology and hepatology 19 37572734
2022 Nur77-Tempo mice reveal T cell steady state antigen recognition. Discovery immunology 19 36704407
2015 HCV core protein promotes hepatocyte proliferation and chemoresistance by inhibiting NR4A1. Biochemical and biophysical research communications 19 26392314
2018 The effect of NR4A1 on APP metabolism and tau phosphorylation. Genes & diseases 18 30591936
2023 Nur77 and PPARγ regulate transcription and polarization in distinct subsets of M2-like reparative macrophages during regenerative inflammation. Frontiers in immunology 17 36936920
2021 Progress and Promise of Nur77-based Therapeutics for Central Nervous System Disorders. Current neuropharmacology 17 32504502
2020 The nuclear receptor NR4A1 is regulated by SUMO modification to induce autophagic cell death. PloS one 17 32210435
2024 Nr4a1 regulates cell-specific transcriptional programs in inhibitory GABAergic interneurons. Neuron 16 38754414
2023 Flavone and Hydroxyflavones Are Ligands That Bind the Orphan Nuclear Receptor 4A1 (NR4A1). International journal of molecular sciences 16 37175855
2015 Histone acetylation regulates orphan nuclear receptor NR4A1 expression in hypercholesterolaemia. Clinical science (London, England : 1979) 16 26396259

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