Affinage

NR0B1

Nuclear receptor subfamily 0 group B member 1 · UniProt P51843

Length
470 aa
Mass
51.7 kDa
Annotated
2026-04-29
100 papers in source corpus 28 papers cited in narrative 28 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NR0B1 (DAX1) is an atypical orphan nuclear receptor that functions as a context-dependent transcriptional regulator central to adrenal and gonadal development, steroidogenesis, and embryonic stem cell pluripotency. It acts predominantly as a transcriptional repressor of SF-1/NR5A1, estrogen receptor, androgen receptor, progesterone receptor, and LRH-1 target genes through direct protein–protein interactions, yet in a dosage-dependent manner it can switch to a coactivator of SF-1 and LRH-1 via the RNA coactivator SRA and TIF2, driving steroidogenic gene expression and Oct4 transcription in ES cells (PMID:19188450, PMID:20943815, PMID:15464421). In ES cells, NR0B1 maintains pluripotency by inhibiting Oct3/4 DNA binding, repressing Gata6 to prevent extra-embryonic endoderm commitment, forming a feedback loop with Esrrb, and serving as a TRIM66-recruited co-repressor of the totipotency gene Dux (PMID:19528230, PMID:25284313, PMID:23508100, PMID:35659877). Loss-of-function mutations cause X-linked adrenal hypoplasia congenita with hypogonadotropic hypogonadism, with disease severity correlating with the degree of impaired repressor activity, while in Ewing sarcoma NR0B1 physically interacts with EWS/FLI to co-regulate oncogenic transcription (PMID:10675358, PMID:19920188, PMID:26464492). NR0B1 also binds RNA and associates with polyribosomes, and disease-associated mutations impair this RNA-binding capacity, indicating an additional post-transcriptional regulatory role (PMID:10848616).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1996 High

    Establishing when and where NR0B1 is expressed during development resolved its candidacy as a regulator of gonadal and adrenal differentiation, showing sexually dimorphic expression patterns consistent with a role in sex determination.

    Evidence In situ hybridization and Northern blot during mouse embryogenesis

    PMID:8630494

    Open questions at the time
    • No functional proof that expression pattern reflects requirement
    • Upstream signals controlling sex-specific expression not identified
  2. 1998 High

    Genetic loss-of-function proved NR0B1 is essential for spermatogenesis but dispensable for ovarian development, establishing its sex-specific in vivo requirement independent of hormonal abnormalities.

    Evidence Cre-mediated Dax1 knockout in mice with hormonal and histological phenotyping

    PMID:9843206

    Open questions at the time
    • Cell-type-specific requirement within the testis not resolved
    • Molecular targets of Dax1 in germ vs. somatic cells unknown
  3. 2000 High

    Discovery that NR0B1 binds RNA and associates with polyribosomes revealed an unexpected post-transcriptional function beyond its known nuclear receptor role, with AHC mutations impairing this activity.

    Evidence Polyribosome fractionation, RNA pull-down, mutagenesis of AHC-associated alleles

    PMID:10848616

    Open questions at the time
    • Specific RNA targets not identified
    • Functional consequence of polyribosome association on translation not demonstrated
  4. 2000 High

    Genotype–phenotype correlation demonstrated that the degree of NR0B1 repressor impairment quantitatively predicts AHC clinical severity, establishing a dose-response relationship between transcriptional function and disease.

    Evidence Reporter assays with missense mutation I439S correlated with milder clinical phenotype

    PMID:10675358

    Open questions at the time
    • Only one intermediate-severity mutation tested
    • In vivo repressor activity not measured
  5. 2001 High

    Sertoli cell-specific transgenic rescue of the Dax1 knockout localized the cell-autonomous requirement for NR0B1 to testicular somatic cells, narrowing the cellular site of action for spermatogenesis support.

    Evidence MIS-promoter-driven human DAX1 transgene in Dax1-null mice with fertility assays

    PMID:11356697

    Open questions at the time
    • Contribution of Leydig cells, peritubular cells, and germ cells not individually resolved
    • Molecular targets of Dax1 in Sertoli cells not identified
  6. 2004 High

    Systematic analysis showed NR0B1 represses not only SF-1 but also ER, AR, PR, and LRH-1 through distinct mechanisms, broadening its role from an SF-1-specific repressor to a general nuclear receptor coregulator.

    Evidence Reporter assays and Co-IP across multiple nuclear receptor systems with AHC mutations

    PMID:15464421

    Open questions at the time
    • Structural basis for receptor-specific repression mechanisms unknown
    • In vivo relevance of ER/AR/PR repression not tested
  7. 2005 High

    Genetic epistasis in double-mutant mice revealed that SF-1 and NR0B1 cooperate rather than simply antagonize each other during testis development, resolving a paradox between in vitro repression data and in vivo biology.

    Evidence SF-1/Dax1 double-knockout mouse analysis with molecular readouts (Dhh, Amh)

    PMID:15829514

    Open questions at the time
    • Biochemical mechanism of cooperation not defined
    • Whether cooperation is direct or via parallel pathways unclear
  8. 2006 Medium

    A disease-causing missense mutation (C200W) that shifts NR0B1 from nucleus to cytoplasm linked nuclear import to transcriptional function and implicated SF-1-dependent and -independent import pathways.

    Evidence Immunofluorescence, in vitro binding, and reporter assays with C200W mutant

    PMID:16459121

    Open questions at the time
    • Nuclear import mechanism not reconstituted
    • Identity of SF-1-independent import factors unknown
  9. 2009 High

    Discovery that NR0B1 can switch from repressor to coactivator of SF-1 via SRA and TIF2 resolved how the same protein supports steroidogenic gene expression in adrenal and Leydig cells.

    Evidence Co-IP, reporter assays, siRNA knockdown of SRA and Dax1 in steroidogenic cells

    PMID:19188450

    Open questions at the time
    • Determinants of repressor-to-coactivator switch not fully defined
    • Whether SRA-dependent coactivation operates in vivo not shown
  10. 2009 High

    NR0B1's interaction with Oct3/4 in ES cells, blocking its DNA binding and causing differentiation upon overexpression, established NR0B1 as a pluripotency regulator beyond its endocrine roles.

    Evidence Co-IP, EMSA, ChIP, and reporter assays in mouse ES cells

    PMID:19528230

    Open questions at the time
    • Physiological context for NR0B1 overexpression during differentiation unclear
    • Whether Oct3/4 inhibition is the primary pluripotency mechanism or one of several not resolved
  11. 2009 High

    Physical interaction between NR0B1 and EWS/FLI with coordinate genome-wide transcriptional regulation established NR0B1 as a functional partner of the Ewing sarcoma oncofusion, required for oncogenic transformation.

    Evidence Reciprocal Co-IP, ChIP, transcriptional profiling, transformation assays with interaction-disrupting mutations

    PMID:19920188

    Open questions at the time
    • Structural interface of the NR0B1–EWS/FLI complex not determined
    • Whether NR0B1 is a therapeutic target in Ewing sarcoma not tested
  12. 2010 High

    NR0B1 coactivates LRH-1-mediated Oct4 transcription via SRA in ES cells, revealing that its coactivator mode extends to pluripotency gene regulation and identifying 288 co-occupied genes.

    Evidence Co-IP, ChIP, reporter assays with knockdown in mouse ES cells

    PMID:20943815

    Open questions at the time
    • Functional consequence of co-occupancy at 288 genes not individually tested
    • Mechanism distinguishing coactivation vs. repression at different LRH-1 targets unknown
  13. 2013 High

    A feedback loop between NR0B1 and Esrrb—NR0B1 represses Esrrb transcriptional activity while Esrrb drives NR0B1 expression—added circuit-level understanding of how pluripotency is balanced in ES cells.

    Evidence Reciprocal Co-IP, ChIP, reporter assays in ES cells

    PMID:23508100

    Open questions at the time
    • Dynamics of the feedback loop during differentiation not characterized
    • Other nodes feeding into this circuit not fully mapped
  14. 2014 High

    Demonstration that NR0B1 acts in parallel with Nanog to prevent extra-embryonic endoderm commitment by directly repressing Gata6 clarified its non-redundant role in ES cell self-renewal.

    Evidence Stable knockdown, ChIP, reporter assays, reprogramming assays in mES cells

    PMID:25284313

    Open questions at the time
    • Whether Gata6 is the sole critical NR0B1 target for lineage restriction not tested
    • In vivo embryonic phenotype of Dax1 loss at this stage not examined
  15. 2015 Medium

    CRISPR knockout in a primate model recapitulated human AHC-HH pathology and implicated Wnt/β-catenin–VEGF signaling as a downstream pathway deregulated by NR0B1 loss in the fetal testis.

    Evidence CRISPR/Cas9 in cynomolgus monkey with histology and pathway analysis

    PMID:26464492

    Open questions at the time
    • Wnt/β-catenin activation could be secondary rather than direct
    • Small cohort inherent to primate CRISPR studies
  16. 2022 High

    Identification of TRIM66 as a recruiter of NR0B1 to the Dux promoter for totipotency suppression in ES cells placed NR0B1 in the chromatin-based repression of the 2-cell-like state, expanding its roles beyond classical nuclear receptor biology.

    Evidence Crystal structure of TRIM66 PHD, Co-IP, ChIP, genetic KO and mutagenesis in mES cells

    PMID:35659877

    Open questions at the time
    • Whether NR0B1 represses other totipotency genes beyond Dux not tested
    • Direct NR0B1–chromatin contacts at Dux not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The specific RNA targets of NR0B1, the structural basis for its repressor-to-coactivator switch, and the mechanism by which it integrates chromatin, transcriptional, and post-transcriptional functions remain unresolved.
  • No RNA targets identified despite demonstrated RNA binding
  • No full-length NR0B1 structure available
  • Mechanism determining whether NR0B1 acts as repressor or coactivator at a given locus undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 8 GO:0098772 molecular function regulator activity 3 GO:0003723 RNA binding 1
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 1 GO:0005840 ribosome 1
Pathway
R-HSA-74160 Gene expression (Transcription) 8 R-HSA-1266738 Developmental Biology 5 R-HSA-1643685 Disease 3 R-HSA-162582 Signal Transduction 2
Partners
ESRRBEWSR1-FLI1NCOA2NR5A1NR5A2POU5F1SRA1TRIM66

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 Ahch (Dax1) knockout in mice reveals that Dax1 is essential for maintenance of spermatogenesis in males (not required for ovarian development or female fertility), with progressive degeneration of the testicular germinal epithelium independent of abnormalities in gonadotropin and testosterone production. Cre-mediated gene disruption in mice, histology, hormone assays Nature genetics High 9843206
1996 Mouse Dax1 is expressed in the first stages of gonadal and adrenal differentiation and in the developing hypothalamus; expression is down-regulated during testis differentiation but persists in the developing ovary, consistent with a role in gonadal sex determination and adrenal function. In situ hybridization, Northern blotting, protein sequence analysis during mouse development Nature genetics High 8630494
2000 DAX-1 protein is both nuclear and cytoplasmic; a significant proportion associates with polyribosomes and is complexed with polyadenylated RNA. DAX-1 directly binds RNA via two cooperative domains, and AHC-associated mutations significantly impair this RNA-binding activity, revealing a post-transcriptional regulatory role. Subcellular fractionation, polyribosome sedimentation, RNA pull-down, immunofluorescence, mutagenesis Molecular and cellular biology High 10848616
2009 Dax-1 can function as a dosage-dependent SF-1 coactivator (in addition to its repressor role) through interaction with the RNA coactivator SRA and the coactivator TIF2. Knockdown of SRA or Dax-1 reduces expression of steroidogenic gene products (StAR, CYP11A1) in adrenal and Leydig cells. A naturally occurring Dax-1 mutation abolishes this coactivation and mislocalizes the mutant Dax-1–TIF2 complex. Co-immunoprecipitation, reporter assays, siRNA knockdown, live-cell imaging Molecular and cellular biology High 19188450
2009 EWS/FLI and NR0B1 physically interact and coordinately regulate gene expression across the genome in Ewing sarcoma. NR0B1 mutations that disrupt this protein-protein interaction have transcriptional consequences and abrogate oncogenic transformation. Co-immunoprecipitation, chromatin immunoprecipitation, transcriptional profiling, mutagenesis, transformation assays Cancer research High 19920188
2009 Dax1 binds Oct3/4 in embryonic stem cells via the POU-specific domain of Oct3/4, abolishes Oct3/4 DNA-binding activity, and inhibits Oct3/4-mediated activation of Nanog and Rex1 promoters. Overexpression of Dax1 causes ES cell differentiation. Co-immunoprecipitation, pulldown, gel-shift (EMSA), ChIP, reporter assays, overexpression/knockdown Molecular and cellular biology High 19528230
2010 Dax1 forms a complex with LRH-1 (NR5A2) in mouse embryonic stem cells and, rather than repressing, coactivates LRH-1-mediated transcription of Oct4 via the RNA coactivator SRA. Dax1 and LRH-1 co-occupy 288 genes involved in mES cell pluripotency. Co-immunoprecipitation, ChIP, luciferase reporter assays, overexpression/knockdown Molecular endocrinology High 20943815
2014 Dax1 acts in parallel with Nanog to maintain mES cell identity; Dax1 is indispensable for self-renewal of Nanog-low cells and prevents extra-embryonic endoderm commitment by directly repressing Gata6 transcription. Stable knockdown, overexpression, ChIP, reporter assays, reprogramming assays Nature communications High 25284313
2013 Dax1 interacts with Esrrb through LXXLL motifs of Dax1 and the activation/ligand-binding domains of Esrrb; Dax1 represses Esrrb transcriptional activity, while Esrrb in turn drives Dax1 transcription via a direct ERRE binding site, forming a regulatory feedback loop in ES cells. Co-immunoprecipitation, pulldown, luciferase reporter assays, ChIP, overexpression/knockdown Molecular and cellular biology High 23508100
2022 TRIM66 recruits DAX1 as a co-repressor to the Dux promoter to suppress the 2-cell-like state in mES cells; TRIM66's repressive effect on Dux is dependent on DAX1. Crystal structure of TRIM66's PHD finger shows it recognizes H3K4-K9me3; mutational evidence confirms its necessity for Dux repression. Crystal structure, Co-IP, ChIP, mutagenesis, chimeric assay, genetic KO Cell stem cell High 35659877
2005 Sf1 and Dax1 function cooperatively in vivo to mediate somatic cell differentiation during testis development (inducing Dhh and Amh expression in Sertoli cells); despite being transcriptional antagonists in vitro, in vivo Sf1/Dax1 double mutant gonads show greater reduction of Dhh and fetal Leydig markers than either single mutant, establishing pathway cooperation. Genetic epistasis (double-mutant mouse analysis), qRT-PCR, immunohistochemistry Development High 15829514
2001 Sertoli cell-specific expression of a human DAX1 transgene (driven by the MIS promoter) in Dax1-null mice partially rescues fertility and sperm function, demonstrating that Dax1 function in Sertoli cells is sufficient to overcome thresholds for sperm production, but full rescue of testicular pathology requires Dax1 expression in other somatic cells. Transgenic rescue, sperm count/motility assays, IVF, histology Endocrinology High 11356697
2000 A novel DAX1 missense mutation (I439S) in the C-terminal domain confers intermediate levels of transcriptional repressor activity compared with classic AHC mutations, correlating with a milder clinical phenotype (delayed-onset adrenal insufficiency, incomplete HH, oligospermia), demonstrating a dose-response between repressor activity and disease severity. Transfection reporter assays, clinical phenotyping, sequencing Journal of Clinical Investigation High 10675358
2004 AHC-associated DAX1 mutations abrogate its ability to act as a transcriptional repressor of SF-1 target genes. DAX1 also functions as a negative coregulator of estrogen receptor (ER), LRH-1, androgen receptor (AR), and progesterone receptor (PR), each by distinct repression mechanisms. Transfection reporter assays, mutagenesis, co-immunoprecipitation Molecular genetics and metabolism High 15464421
2002 DAX-1 inhibits cAMP/SF-1-induced aromatase P450 promoter activity in a dose-dependent fashion in cultured human endometriotic and endometrial stromal cells, acting through the SF-1 binding site at -136/-124 bp of the P450arom promoter. Transfection reporter assays, site-directed mutagenesis, immunohistochemistry Journal of Clinical Endocrinology and Metabolism Medium 12213901
2006 DAX1 up-regulation in Ewing tumors is dependent on EWS/FLI1 expression (not wild-type FLI1); silencing EWS/FLI1 by RNAi markedly reduces DAX1 mRNA and protein levels, placing NR0B1 as a downstream transcriptional target of the EWS/FLI1 oncofusion. cDNA arrays, inducible expression systems, RNAi knockdown, Western blot International journal of cancer Medium 16206264
2002 Androgen receptor (AR) down-regulates Dax-1 gene transcription mediated by Ad4BP/SF-1 in a ligand-dependent manner through a direct interaction between AR and Ad4BP/SF-1; AR suppression of Dax-1 does not require direct AR DNA binding. RT-PCR, Western blotting, co-immunoprecipitation, gonadectomy/steroid replacement experiments, promoter assays Genes to cells Medium 12081648
2015 TNF-α activates DAX-1 expression via JNK/ERK MAP kinase pathways in Leydig cells; siRNA-mediated knockdown of DAX-1 restores steroidogenic protein expression in TNF-α-treated Leydig cells, placing DAX-1 as a downstream mediator of TNF-α-induced suppression of steroidogenesis. siRNA transfection, RT-PCR, Western blotting, kinase inhibitors Inflammation research Medium 26047595
2009 Retinoic acid induces nNOS transcription in human neuroblastoma cells through a PI3K/Akt/DAX1-dependent pathway: RA increases DAX1 expression via PI3K/Akt signaling, and upregulated DAX1 in turn drives nNOS gene transcription. siRNA knockdown, PI3K/Akt inhibitors, reporter assays, Western blotting American journal of physiology — Cell physiology Medium 19726747
2006 A DAX1 missense mutation in the hinge region (C200W) shifts subcellular localization from nucleus to cytoplasm; the import defect correlates with impaired transcriptional repression activity. Import of DAX1 into the nucleus involves a direct interaction with SF1; the C200W mutant retains SF1-binding but shows reduced nuclear import, suggesting SF1-independent interactions also contribute. Immunofluorescence, in vitro binding assays, reporter assays, mutagenesis Molecular genetics and metabolism Medium 16459121
2004 An alternatively spliced isoform of NR0B1, designated NR0B1A (encoding DAX1A of 400 aa vs. 470 aa for DAX1), is expressed in adrenal gland, testis, ovary, and pancreas, requiring reinterpretation of previous NR0B1 knockout and expression experiments. RT-PCR, cDNA sequencing, EST analysis Molecular genetics and metabolism Low 15589120
2015 CRISPR/Cas9-mediated Dax1 knockout in cynomolgus monkey produces defects in adrenal development and abnormal testis architecture (small cords, fibrosis) closely resembling human AHC-HH; upregulation of Wnt/β-catenin–VEGF signaling is detected in the fetal Dax1-deficient testis, implicating this pathway in AHC-HH pathogenesis. CRISPR/Cas9 genome editing, histology, immunostaining, pathway analysis Human molecular genetics Medium 26464492
2009 NR0B1 reduction in lung adenocarcinoma cell lines reduces invasion, colony formation, and tumorigenicity in NOD/SCID mice, establishing a functional role for NR0B1 in the malignant potential of lung adenocarcinoma. siRNA/shRNA knockdown, invasion assays, colony formation, xenograft American journal of pathology Medium 19644015
2010 LRH-1 binds the -128 nuclear receptor site of the Dax1 promoter to drive Dax1 expression in mES cells; Nanog binds an intronic enhancer and cooperates with LRH-1 to regulate Dax1 transcription. Luciferase reporter assays, EMSA, ChIP, overexpression/knockdown Molecular and cellular endocrinology Medium 20937355
2014 NR0B1 GGAA-microsatellite polymorphisms in the promoter modulate EWS/FLI-mediated NR0B1 gene expression in a non-linear, bimodal fashion dependent on the number of GGAA motifs; maximal expression occurs with 20–26 GGAA repeats, linking microsatellite length to transcriptional output. Reporter assays with synthetic microsatellite constructs, genotyping of tumor samples PloS one Medium 25093581
2009 X-linked congenital AHC can be caused by a noncoding mutation: an X-chromosome inversion disrupts a conserved enhancer 4 kb upstream of NR0B1 that contains an SF-1 binding site required for NR0B1 transcriptional activation; reporter constructs lacking this element are unresponsive to SF-1. Linkage analysis, breakpoint mapping, reporter assays, immunohistochemistry Journal of Clinical Endocrinology and Metabolism Medium 19773398
2006 DAX-1 expression increases upon EGF withdrawal-induced differentiation of mammary epithelial HC11 cells, and DAX-1 cytoplasmic levels increase as cells differentiate (nuclear in virgin gland, cytoplasmic in lactating gland). Cotransfection of DAX-1 inhibits estrogen response element-reporter activity and ER-regulated gene expression driven by ERα or ERβ. Western blot, qRT-PCR, confocal microscopy, transfection reporter assays Endocrinology Medium 16627587
2020 Triclosan-induced suppression of testicular P450c17 involves DAX1: TCS-induced miR-142-5p inhibits JAK1/STAT1 → Sp1 → DNMT1 pathway, leading to increased DAX1 transcription which in turn represses steroidogenic P450c17. Bidirectional Co-IP, ChIP, siRNA, DNMT inhibition, qPCR, Western blot Science of the total environment Low 32084696

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Investigating intestinal inflammation in DSS-induced model of IBD. Journal of visualized experiments : JoVE 535 22331082
1998 Role of Ahch in gonadal development and gametogenesis. Nature genetics 341 9843206
1996 Mouse Dax1 expression is consistent with a role in sex determination as well as in adrenal and hypothalamus function. Nature genetics 307 8630494
2004 Molecular mechanisms of DAX1 action. Molecular genetics and metabolism 159 15464421
2015 DAX-1 (NR0B1) and steroidogenic factor-1 (SF-1, NR5A1) in human disease. Best practice & research. Clinical endocrinology & metabolism 154 26303087
2018 Protective Effect of Naringin on DSS-Induced Ulcerative Colitis in Mice. Journal of agricultural and food chemistry 152 30472831
2014 Chemerin aggravates DSS-induced colitis by suppressing M2 macrophage polarization. Cellular & molecular immunology 148 24727542
2000 A novel mutation in DAX1 causes delayed-onset adrenal insufficiency and incomplete hypogonadotropic hypogonadism. The Journal of clinical investigation 127 10675358
2001 Phenotypic spectrum of mutations in DAX-1 and SF-1. Molecular and cellular endocrinology 105 11738790
2013 Paeoniflorin abrogates DSS-induced colitis via a TLR4-dependent pathway. American journal of physiology. Gastrointestinal and liver physiology 104 24232001
2000 Orphan receptor DAX-1 is a shuttling RNA binding protein associated with polyribosomes via mRNA. Molecular and cellular biology 98 10848616
2020 Cow and Human Milk-Derived Exosomes Ameliorate Colitis in DSS Murine Model. Nutrients 96 32858892
2009 Dax-1 and steroid receptor RNA activator (SRA) function as transcriptional coactivators for steroidogenic factor 1 in steroidogenesis. Molecular and cellular biology 91 19188450
2000 Temperature-dependent sex determination in the American alligator: expression of SF1, WT1 and DAX1 during gonadogenesis. Gene 87 10675033
2013 Dietary selenium deficiency exacerbates DSS-induced epithelial injury and AOM/DSS-induced tumorigenesis. PloS one 83 23861820
1995 Diagnosis of X-linked adrenal hypoplasia congenita by mutation analysis of the DAX1 gene. JAMA 81 7609262
2001 Mutations in NR0B1 (DAX1) and NR5A1 (SF1) responsible for adrenal hypoplasia congenita. Human mutation 76 11748841
2009 EWS/FLI and its downstream target NR0B1 interact directly to modulate transcription and oncogenesis in Ewing's sarcoma. Cancer research 75 19920188
2015 CRISPR/Cas9-mediated Dax1 knockout in the monkey recapitulates human AHC-HH. Human molecular genetics 68 26464492
2020 The ameliorative effect of Lactobacillus plantarum-12 on DSS-induced murine colitis. Food & function 67 32458908
2005 Nuclear receptors Sf1 and Dax1 function cooperatively to mediate somatic cell differentiation during testis development. Development (Cambridge, England) 67 15829514
2006 The orphan nuclear receptor DAX1 is up-regulated by the EWS/FLI1 oncoprotein and is highly expressed in Ewing tumors. International journal of cancer 66 16206264
1989 In vivo circumvention of vincristine resistance in mice with P388 leukemia using a novel compound, AHC-52. Cancer research 65 2924316
2005 DAX1 origin, function, and novel role. Molecular genetics and metabolism 60 16146703
1996 The gene responsible for adrenal hypoplasia congenita, DAX-1, encodes a nuclear hormone receptor that defines a new class within the superfamily. Recent progress in hormone research 59 8701082
2002 WT1 and DAX-1 inhibit aromatase P450 expression in human endometrial and endometriotic stromal cells. The Journal of clinical endocrinology and metabolism 55 12213901
1999 Mutational analysis of DAX1 in patients with hypogonadotropic hypogonadism or pubertal delay. The Journal of clinical endocrinology and metabolism 55 10599708
2011 Hypogonadotropic hypogonadism in subjects with DAX1 mutations. Molecular and cellular endocrinology 54 21672607
2009 Dax1 binds to Oct3/4 and inhibits its transcriptional activity in embryonic stem cells. Molecular and cellular biology 54 19528230
2022 Atractylodes lancea Rhizoma Attenuates DSS-Induced Colitis by Regulating Intestinal Flora and Metabolites. The American journal of Chinese medicine 53 35114907
2017 Aryl hydrocarbon receptor inhibits inflammation in DSS‑induced colitis via the MK2/p‑MK2/TTP pathway. International journal of molecular medicine 53 29207040
2004 Sex determination: a 'window' of DAX1 activity. Trends in endocrinology and metabolism: TEM 53 15046740
2014 The role of CXCR3 in DSS-induced colitis. PloS one 52 24992040
2009 ROS, Hsp27, and IKKbeta mediate dextran sodium sulfate (DSS) activation of IkappaBa, NFkappaB, and IL-8. Inflammatory bowel diseases 52 19085995
2007 DAX1: Increasing complexity in the roles of this novel nuclear receptor. Molecular and cellular endocrinology 51 17210221
2014 Dax1 and Nanog act in parallel to stabilize mouse embryonic stem cells and induced pluripotency. Nature communications 50 25284313
2014 The oxysterol receptor LXRβ protects against DSS- and TNBS-induced colitis in mice. Mucosal immunology 49 24803164
2000 Cloning and expression of a DAX1 homologue in the chicken embryo. Journal of molecular endocrinology 49 10656994
2002 Sexually dimorphic expression of Dax-1 in the adrenal cortex. Genes to cells : devoted to molecular & cellular mechanisms 48 12081648
2015 The anti-inflammatory effect and potential mechanism of cardamonin in DSS-induced colitis. American journal of physiology. Gastrointestinal and liver physiology 47 26251468
2009 Clinical and genetic heterogeneity of congenital adrenal hypoplasia due to NR0B1 gene mutations. Clinical endocrinology 47 19508677
2020 Jmjd3 regulates inflammasome activation and aggravates DSS-induced colitis in mice. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 46 31971317
2021 Anthocyanin-containing purple potatoes ameliorate DSS-induced colitis in mice. The Journal of nutritional biochemistry 45 33705951
2010 Dax1 up-regulates Oct4 expression in mouse embryonic stem cells via LRH-1 and SRA. Molecular endocrinology (Baltimore, Md.) 44 20943815
2016 Nicotine protects against DSS colitis through regulating microRNA-124 and STAT3. Journal of molecular medicine (Berlin, Germany) 41 27709266
1998 DAX-1 expression in human adrenocortical neoplasms: implications for steroidogenesis. The Journal of clinical endocrinology and metabolism 41 9661652
1999 DAX-1, an 'antitestis' gene. Cellular and molecular life sciences : CMLS 39 10412368
2001 Sertoli cell-specific rescue of fertility, but not testicular pathology, in Dax1 (Ahch)-deficient male mice. Endocrinology 38 11356697
2024 Puerarin ameliorates colitis by direct suppression of macrophage M1 polarization in DSS mice. Phytomedicine : international journal of phytotherapy and phytopharmacology 37 39326132
2010 Role of DAX-1 (NR0B1) and steroidogenic factor-1 (NR5A1) in human adrenal function. Endocrine development 37 21164257
2003 Mutations in the SRY, DAX1, SF1 and WNT4 genes in Brazilian sex-reversed patients. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 37 14689056
2022 Intestinal Epithelial AMPK Deficiency Causes Delayed Colonic Epithelial Repair in DSS-Induced Colitis. Cells 35 35203241
2017 Prdx6 Deficiency Ameliorates DSS Colitis: Relevance of Compensatory Antioxidant Mechanisms. Journal of Crohn's & colitis 34 28199527
1999 Novel DAX1 mutations in X-linked adrenal hypoplasia congenita and hypogonadotrophic hypogonadism. Clinical endocrinology 34 10341858
2019 Daucosterol suppresses dextran sulfate sodium (DSS)-induced colitis in mice. International immunopharmacology 33 30978647
2024 Macrophage Tim-3 maintains intestinal homeostasis in DSS-induced colitis by suppressing neutrophil necroptosis. Redox biology 31 38330550
2014 Clinical and biochemical function of polymorphic NR0B1 GGAA-microsatellites in Ewing sarcoma: a report from the Children's Oncology Group. PloS one 31 25093581
2006 DAX1 and X-linked adrenal hypoplasia congenita: clinical and molecular analysis in five patients. European journal of endocrinology 31 16645015
2013 Dax1 associates with Esrrb and regulates its function in embryonic stem cells. Molecular and cellular biology 30 23508100
2009 Tumorigenic role of orphan nuclear receptor NR0B1 in lung adenocarcinoma. The American journal of pathology 30 19644015
2023 Ononin alleviates DSS-induced colitis through inhibiting NLRP3 inflammasome via triggering mitophagy. Immunity, inflammation and disease 27 36840499
2015 Effect of curcumin on p38MAPK expression in DSS-induced murine ulcerative colitis. Genetics and molecular research : GMR 27 25966111
2010 Seven novel DAX1 mutations with loss of function identified in Chinese patients with congenital adrenal hypoplasia. The Journal of clinical endocrinology and metabolism 27 20573681
2010 LRH-1 and Nanog regulate Dax1 transcription in mouse embryonic stem cells. Molecular and cellular endocrinology 27 20937355
2018 Inhibition of NADPH oxidase activities ameliorates DSS-induced colitis. Biochemical pharmacology 26 30321511
2009 Retinoic acid-induced nNOS expression depends on a novel PI3K/Akt/DAX1 pathway in human TGW-nu-I neuroblastoma cells. American journal of physiology. Cell physiology 26 19726747
2010 Targeting DAX-1 in embryonic stem cells and cancer. Expert opinion on therapeutic targets 25 20055716
2023 Geniposidic acid attenuates DSS-induced colitis through inhibiting inflammation and regulating gut microbiota. Phytotherapy research : PTR 23 37098758
2022 A TRIM66/DAX1/Dux axis suppresses the totipotent 2-cell-like state in murine embryonic stem cells. Cell stem cell 23 35659877
2022 Gpr174 Knockout Alleviates DSS-Induced Colitis via Regulating the Immune Function of Dendritic Cells. Frontiers in immunology 23 35669778
2008 Nuclear receptor DAX1 in human prostate cancer: a novel independent biological modulator. Endocrine journal 23 18827407
2018 Nicotine treatment ameliorates DSS-induced colitis by suppressing MAdCAM-1 expression and leukocyte recruitment. Journal of leukocyte biology 22 29901817
2015 TNF-α-mediated suppression of Leydig cell steroidogenesis involves DAX-1. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 22 26047595
2004 NR0B1A: an alternatively spliced form of NR0B1. Molecular genetics and metabolism 22 15589120
2020 miR-142-5p/DAX1-dependent regulation of P450c17 contributes to triclosan-mediated testosterone suppression. The Science of the total environment 21 32084696
2019 Electroacupuncture and Moxibustion Improved Anxiety Behavior in DSS-Induced Colitis Mice. Gastroenterology research and practice 21 30881446
2000 Primate DAX1, SRY, and SOX9: evolutionary stratification of sex-determination pathway. American journal of human genetics 20 11112659
2011 BTZO-15, an ARE-activator, ameliorates DSS- and TNBS-induced colitis in rats. PloS one 19 21853095
2006 A familial missense mutation in the hinge region of DAX1 associated with late-onset AHC in a prepubertal female. Molecular genetics and metabolism 19 16459121
2019 MLKL deficiency inhibits DSS-induced colitis independent of intestinal microbiota. Molecular immunology 18 30738250
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