Affinage

AHR

Aryl hydrocarbon receptor · UniProt P35869

Length
848 aa
Mass
96.1 kDa
Annotated
2026-06-09
100 papers in source corpus 24 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AHR is a ligand-activated bHLH-PAS transcription factor that links sensing of xenobiotic and endogenous small molecules to a broad transcriptional program governing detoxification, tissue homeostasis, and immunity (PMID:12573486, PMID:28146477). In the unliganded state AHR resides in the cytoplasm within a chaperone complex with Hsp90 and the immunophilin AIP/XAP2; AIP docks onto the Hsp90 C-terminus through its tetratricopeptide-repeat domain and contacts AHR through its alpha-helical C-terminus, stabilizing the ligand-binding-competent PAS-B domain (PMID:11469723, PMID:10961990, PMID:36649707). Cryo-EM of the Hsp90–AHR–p23 complex resolved a conserved AHR 'bridge motif' that inserts into the Hsp90 dimeric lumen and showed that XAP2 stabilizes ligand-free PAS-B, with DE-loop and pocket residues forming the ligand-binding cavity (PMID:36649707). Upon ligand binding AHR translocates to the nucleus—a redistribution controlled by phosphorylation near its NLS/NES—dissociates from Hsp90, heterodimerizes with ARNT, and binds xenobiotic response elements to drive transcription of CYP1A1 and other targets, after which nuclear AHR is degraded by the ubiquitin–26S proteasome to limit signaling duration (PMID:12573486, PMID:11469723, PMID:18983832). The CYP1A1 enzymes it induces in turn deplete endogenous ligands, forming a feedback loop that sets AHR activity in vivo (PMID:28146477), and AHR activity is further tuned by competition with HIF-1α for shared ARNT and by ligand supply from tryptophan-catabolizing pathways such as IL4I1 (PMID:11382553, PMID:32818467). Beyond canonical transcription, ligand-activated AHR serves as the substrate-recognition subunit of a CUL4B E3 ubiquitin ligase that targets ERα and AR for proteolysis (PMID:18838062). Across tissues AHR executes protective and differentiation programs: it sustains intestinal ILC3/Th17 immunity (PMID:28146477), drives NK cell migration via ASB2-mediated filamin A degradation (PMID:33717133), promotes SIRT1-dependent keratinocyte differentiation by repressing glycolytic genes SLC2A1 and ENO1 (PMID:30393078), and in endothelium senses dietary metabolites to maintain vascular quiescence and barrier integrity, engaging the apelin-APJ system to protect against influenza- and infection-induced damage (PMID:37587341, PMID:37586410). A homozygous stop-gain mutation (p.Q621*) in AHR causes autosomal recessive foveal hypoplasia and infantile nystagmus, and AHR-null mice show defective optic nerve myelination, establishing AHR as a physiological regulator of myelination (PMID:31009037, PMID:28851966).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 2000 High

    Established how AHR is held in a ligand-competent state, defining the architecture of the cytoplasmic chaperone complex through which AHR is folded and primed.

    Evidence Reticulocyte-lysate binding assays with AIP/Hsp90 mutagenesis and geldanamycin/ATP sensitivity tests

    PMID:10961990

    Open questions at the time
    • Stoichiometry and dynamics of the full complex in cells not resolved
    • Did not show how ligand binding triggers complex dissociation
  2. 2001 High

    Resolved the lifecycle of AHR signaling — cytoplasmic chaperoning for ligand competence followed by proteasomal degradation of activated nuclear receptor — establishing that signal duration is actively limited.

    Evidence Biochemical characterization, proteasome inhibition, and receptor turnover assays

    PMID:11469723

    Open questions at the time
    • E3 ligase responsible for activated-AHR turnover not identified here
    • Coupling between transcription and degradation not mechanistically dissected
  3. 2001 Medium

    Showed that AHR and HIF-1α are not independent pathways but compete for the shared dimerization partner ARNT, explaining crosstalk between xenobiotic and hypoxic signaling.

    Evidence Reporter assays, EMSA at DRE/HIF-1 sites, and enzyme activity assays across multiple cell lines

    PMID:11382553

    Open questions at the time
    • Whether competition occurs at ARNT abundance or DNA-binding step not fully separated
    • In vivo physiological relevance not addressed
  4. 2003 High

    Consolidated the canonical mechanism: ligand-triggered nuclear translocation, Hsp90 dissociation, ARNT heterodimerization, and XRE-driven transcription of CYP1A1.

    Evidence Mechanistic CYP1A1 induction studies with ligand binding, translocation, and DNA-binding assays

    PMID:12573486

    Open questions at the time
    • Full set of physiological target genes not enumerated
    • Tissue-specific cofactor requirements not defined
  5. 2008 High

    Revealed a non-transcriptional function: ligand-activated AHR assembles a CUL4B E3 ligase and acts as a substrate-recognition subunit to degrade ERα and AR, uncoupling AHR action from DNA binding.

    Evidence Co-immunoprecipitation, ubiquitination, and proteasome-dependent degradation assays

    PMID:18838062

    Open questions at the time
    • Determinants of substrate selection by the AHR-CUL4B complex not mapped
    • Physiological contexts where this dominates over transcription unclear
  6. 2008 Medium

    Mapped how AHR subcellular distribution is set, showing phosphorylation near NLS/NES and cell density control localization and target gene transactivation.

    Evidence Subcellular fractionation, live-cell imaging, NLS/NES mutagenesis, and phosphorylation studies

    PMID:18983832

    Open questions at the time
    • Kinases acting on the NLS/NES not all identified
    • Quantitative contribution relative to ligand-driven import unclear
  7. 2008 Medium

    Identified a non-canonical AHR signaling arm in which agonists drive MMP-1 expression through calcium/CaMKII/MAPK and AP-1 rather than XRE binding.

    Evidence Reporter assays, pharmacological inhibitors, and kinase activity assays in bronchial epithelial cells

    PMID:24469321

    Open questions at the time
    • Whether AHR protein directly initiates the calcium signal is not established
    • In vivo relevance to airway remodeling untested
  8. 2008 Low

    Provided evidence for ligand-independent activation, with PKA rendering AHR nuclear and activating target genes by a route distinct from exogenous ligand.

    Evidence PKA activation/inhibition studies and nuclear import assays

    PMID:19013136

    Open questions at the time
    • Single lab with limited mechanistic follow-up; molecular target of PKA on AHR not defined
    • Physiological trigger for this mode unknown
  9. 2017 High

    Demonstrated in vivo that CYP1A1 enzymes form a feedback loop depleting endogenous AHR ligands, linking AHR ligand availability to intestinal ILC3/Th17 immunity and infection resistance.

    Evidence Transgenic mice with constitutive or intestinal Cyp1a1, immune phenotyping, infection challenge, dietary rescue

    PMID:28146477

    Open questions at the time
    • Identity of the depleted endogenous ligands not fully defined
    • Tissue-by-tissue ligand turnover not quantified
  10. 2017 Medium

    Showed a ligand-independent, tumor-suppressive AHR function through direct interaction with Rb1 to restrain E2F-driven cell cycle progression.

    Evidence Overexpression/knockdown, AHR–Rb1 co-IP, and cell cycle analysis in pituitary GH3 cells

    PMID:28649092

    Open questions at the time
    • Reciprocal validation and structural basis of AHR–Rb1 binding lacking
    • Generality beyond pituitary cells untested
  11. 2017 Medium

    Linked AHR to myelin biology, showing AHR-deficient optic nerves have altered myelin lipid composition and reduced MAG with inflammation.

    Evidence Ahr-/- mice with lipid analysis, MAG immunostaining, and cytokine profiling

    PMID:28851966

    Open questions at the time
    • Direct AHR target genes driving myelination not identified
    • Cell-autonomous versus inflammatory contributions not separated
  12. 2019 High

    Established AHR as a human disease gene, with a stop-gain mutation causing recessive foveal hypoplasia/nystagmus and mouse knockouts confirming a physiological role in optic nerve myelination.

    Evidence Whole exome sequencing in humans plus Ahr-/- mouse optic nerve histology

    PMID:31009037

    Open questions at the time
    • Mechanism connecting AHR loss to foveal hypoplasia not defined
    • Whether myelination defect explains the nystagmus fully unresolved
  13. 2019 Medium

    Connected AHR loss to developmental endocrine phenotypes via Notch and ERα dysregulation in testis and mammary tissue.

    Evidence Ahr-/- mice with gene expression, histology, and serum hormone measurements

    PMID:27688768

    Open questions at the time
    • Direct versus indirect regulation of Notch genes not distinguished
    • Relationship to the AHR-CUL4B/ERα degradation mechanism not integrated
  14. 2020 Medium

    Identified IL4I1 tryptophan catabolism as an endogenous source of AHR agonists driving tumor cell motility and immune suppression.

    Evidence Pan-tissue AHR signature, biochemical metabolite assays, and IL4I1-manipulated CLL mouse model

    PMID:32818467

    Open questions at the time
    • Relative contribution of indoles versus kynurenic acid in vivo unclear
    • Direct AHR target genes mediating motility not mapped
  15. 2021 Medium

    Defined how AHR controls NK cell motility, transcriptionally inducing ASB2 to degrade filamin A and enable migration and tumor infiltration.

    Evidence Ahr-/- mice, AHR agonist treatment, ASB2 knockdown, and filamin A degradation/in vivo migration assays

    PMID:33717133

    Open questions at the time
    • Direct AHR binding at the ASB2 locus not shown
    • Single lab without reciprocal genetic confirmation
  16. 2021 Medium

    Showed AHR is required for aflatoxin B1 hepatotoxicity, with AFB1 binding the AHR N-terminus to drive nuclear translocation and P450 induction generating DNA adducts.

    Evidence Genome-wide CRISPR screen, AHR-knockout cells, adduct quantification, and translocation assays

    PMID:34373448

    Open questions at the time
    • Structural basis of N-terminal AFB1 binding not resolved
    • Whether this differs from canonical PAS-B ligand engagement unclear
  17. 2021 Medium

    Implicated AHR in coronavirus infection, with viral activation of AHR and AHR inhibition suppressing HCoV-229E and SARS-CoV-2 replication.

    Evidence In vitro viral replication assays with AHR inhibitors and patient lung scRNA-seq

    PMID:34446714

    Open questions at the time
    • Mechanism by which AHR signaling supports viral replication not defined
    • Causality in patients inferred from expression only
  18. 2022 Medium

    Established a metabolic logic for AHR-driven keratinocyte differentiation: AHR represses glycolytic genes to raise SIRT1 in a pyruvate-dependent manner.

    Evidence ChIP, metabolic assays, protein measurements, and SIRT1 loss-of-function in keratinocytes

    PMID:30393078

    Open questions at the time
    • Direct repression mechanism at SLC2A1/ENO1 versus indirect effects not fully separated
    • In vivo skin relevance not tested in this study
  19. 2022 Medium

    Linked UVB-induced DNA damage to AHR-driven skin aging, showing AHR cooperates with SP1 to induce MMP2/MMP11 and that AHR antagonists reduce wrinkling.

    Evidence HaCaT mechanistic studies with AHR/SP1 inhibition, reporter assays, and a mouse wrinkle model

    PMID:35316219

    Open questions at the time
    • Direct AHR–SP1 promoter co-occupancy not structurally defined
    • Selectivity for MMP2/MMP11 over MMP1/3 mechanistically unexplained
  20. 2023 High

    Provided the structural basis of chaperone-held AHR, resolving the bridge motif inserting into Hsp90 and XAP2 stabilization of ligand-free PAS-B.

    Evidence Cryo-EM of Hsp90–AHR–p23 (±XAP2) with mutagenesis

    PMID:36649707

    Open questions at the time
    • Conformational changes accompanying ligand binding and release not captured
    • Structure of the active AHR–ARNT–DNA complex not resolved here
  21. 2023 High

    Defined endothelial AHR as a sensor of dietary metabolites that maintains vascular quiescence and barrier integrity, protecting against influenza and enteric infection.

    Evidence Endothelial-specific AHR conditional knockouts, single-cell atlases, permeability assays, and infection challenge

    PMID:37586410 PMID:37587341

    Open questions at the time
    • Specific dietary ligands sensed in each vascular bed not fully identified
    • Direct target genes downstream of apelin-APJ engagement not enumerated
  22. 2023 Medium

    Showed nutrient context tunes AHR sensitivity, with tryptophan deprivation inducing AHR and GCN2-dependent LAT1 to amplify kynurenine-driven AHR signaling and Treg differentiation.

    Evidence RT-qPCR, western blot, Ahr-variant and knockout T cells, and in vitro Treg differentiation

    PMID:37344101

    Open questions at the time
    • Mechanism of tryptophan-depletion-induced AHR overexpression not defined
    • In vivo tumor relevance not directly tested here
  23. 2024 Medium

    Connected AHR to macrophage-mediated immune suppression, showing AHR induces ALKAL1 to promote MerTK phosphorylation and immunosuppressive polarization.

    Evidence scRNA-seq, AHR antagonist studies, adoptive transfer, and targeted nanoparticle delivery in vivo

    PMID:39365866

    Open questions at the time
    • Direct AHR occupancy at ALKAL1 not shown
    • Generalizability across tumor types not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How AHR integrates its canonical XRE-transcription, CUL4B-E3-ligase, and ligand-independent (Rb1/PKA) modes into a unified tissue-specific decision, and which endogenous ligands govern each context, remains unresolved.
  • No structure of the active AHR-ARNT-DNA complex in the timeline
  • The endogenous ligand repertoire across tissues is incompletely defined
  • Determinants selecting transcriptional versus E3-ligase output are unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 3 GO:0003677 DNA binding 2 GO:0140299 molecular sensor activity 2 GO:0016874 ligase activity 1 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005829 cytosol 3 GO:0005634 nucleus 2
Pathway
R-HSA-168256 Immune System 4 R-HSA-1266738 Developmental Biology 3 R-HSA-392499 Metabolism of proteins 2 R-HSA-74160 Gene expression (Transcription) 1
Partners
AIPARARNTCUL4BESR1HSP90P23RB1
Complex memberships
AHR–ARNT heterodimerCUL4B^AHR E3 ubiquitin ligaseHsp90–AHR–AIP/XAP2–p23 cytoplasmic chaperone complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 Ligand-bound AHR translocates from cytoplasm to nucleus, dissociates from Hsp90, and heterodimerizes with ARNT; the AHR/ARNT heterodimer binds XRE (xenobiotic response elements) in the promoter of target genes such as CYP1A1 to drive their transcription. Mechanistic studies of CYP1A1 induction; ligand binding, nuclear translocation, and DNA-binding assays Biochimica et biophysica acta High 12573486
2001 In the cytoplasm, AHR interacts with Hsp90 and the immunophilin chaperone AIP (AhR-interacting protein) for proper folding and ligand-binding competence; after nuclear entry, agonist-activated AHR is degraded via the ubiquitin–26S proteasome pathway, limiting the duration of transcriptional activation. Biochemical characterization, proteasome inhibition experiments, receptor turnover assays Current drug metabolism High 11469723
2000 AIP binds to AHR in an Hsp90-dependent manner: AIP binds the C-terminus of Hsp90 via its tetratricopeptide repeat domain (mutation K266A abolishes Hsp90 binding and reduces AHR binding by 75–80%), while the alpha-helical C-terminus of AIP is absolutely required for AHR interaction but not for Hsp90 binding. Hsp90 is required for AHR–AIP complex formation. Reticulocyte lysate binding assays, site-directed mutagenesis, geldanamycin/ATP sensitivity tests, deletion analysis The Journal of biological chemistry High 10961990
2008 Ligand-activated AHR assembles a CUL4B-based E3 ubiquitin ligase complex (CUL4B^AHR), in which AHR acts as a substrate-recognition subunit to recruit estrogen receptor α (ERα) and androgen receptor (AR) for ubiquitin-mediated proteolysis, defining a non-transcriptional role for AHR as a ligand-dependent E3 ubiquitin ligase. Co-immunoprecipitation, ubiquitination assays, proteasome-dependent degradation assays Biochemical pharmacology High 18838062
2008 AHR possesses a functional nuclear localization signal (NLS) and a nuclear export signal (NES); phosphorylation of residues near these signals controls AHR's distribution between cytoplasm and nucleus. Cell density modulates both AHR intracellular localization and its transactivation of target genes including the transcriptional repressor Slug. Subcellular fractionation, live-cell imaging, phosphorylation studies, NLS/NES mutagenesis Biochemical pharmacology Medium 18983832
2001 AHR and HIF-1α signaling pathways mutually repress each other by competing for the shared partner ARNT: TCDD-activated AHR reduced hypoxia-inducible reporter activity, and hypoxia-mimicking agents reduced AHR-mediated CYP1A1 activity and DRE-binding; the interaction is attributable to changes in DNA-binding activity at DRE and HIF-1 binding sites. Reporter gene assays, EMSA (DNA-binding assays), enzyme activity assays in multiple cell lines Environmental toxicology and pharmacology Medium 11382553
2008 AHR agonists increase MMP-1 expression in bronchial epithelial cells via a non-canonical AHR pathway: AHR agonists elevate cytosolic calcium, activating CaMKII, which activates MAPK pathways, phosphorylating c-Jun, c-Fos, and ATF-2, which bind AP-1 elements in the MMP-1 promoter; upregulated MMP-1 further activates MMP-2 and MMP-9. Reporter assays, pharmacological inhibitors, kinase activity assays, ChIP-like promoter analysis Journal of molecular medicine (Berlin, Germany) Medium 24469321
2017 Constitutive expression of Cyp1a1 in mice depletes endogenous AHR ligands, generating a quasi-AHR-deficient state with loss of AHR-dependent ILC3 and Th17 cells and increased susceptibility to enteric infection, demonstrating that CYP1A1 enzymes act as a feedback mechanism regulating AHR ligand availability in vivo. Transgenic mouse model (constitutive Cyp1a1 expression throughout body or restricted to intestinal epithelium), immune cell phenotyping, infection challenge Nature High 28146477
2020 IL4I1 (interleukin-4-induced-1) activates AHR through generation of indole metabolites and kynurenic acid from tryptophan catabolism, promoting cancer cell motility and suppression of adaptive immunity. Pan-tissue AHR signature analysis, biochemical assays of IL4I1 metabolite production, mouse model of CLL with IL4I1 manipulation Cell Medium 32818467
2023 Cryo-EM structures of the Hsp90–AHR–p23 complex (with or without XAP2) resolved the mouse AHR PAS-B domain; a highly conserved 'bridge motif' of AHR is responsible for interaction with the Hsp90 dimeric lumen; ligand-free AHR PAS-B is stabilized by XAP2 binding; conserved DE-loop residues and pocket inner residues are important for ligand binding. Cryo-EM structure determination, mutagenesis, protein purification Structure (London, England : 1993) High 36649707
2021 AHR regulates NK cell migration via transcriptional induction of ASB2, which promotes ubiquitin-mediated degradation of filamin A; loss of AHR reduces ASB2 expression, stabilizes filamin A, and impairs NK cell migration and tumor infiltration in vivo. Ahr-/- mouse model, gene expression analysis, AHR agonist treatment, ASB2 knockdown, filamin A degradation assays, in vivo tumor migration assay Frontiers in immunology Medium 33717133
2022 AHR activation in keratinocytes promotes SIRT1-dependent differentiation by repressing glycolysis: AHR binds and reduces expression of the glucose transporter SLC2A1 and glycolytic enzyme ENO1, lowering glucose uptake and ATP; this metabolic shift increases SIRT1 protein levels in a pyruvate-dependent manner, and SIRT1 is required for AHR-induced keratinocyte differentiation. ChIP, qPCR, metabolic assays (glucose uptake, pyruvate/lactate), protein level measurements, pharmacological inhibitors, SIRT1 loss-of-function The Journal of investigative dermatology Medium 30393078
2019 AHR loss-of-function in Ahr-/- mice causes dysregulation of Notch and ERα signaling: reduced expression of Notch1, Notch3, and their target HES1 leads to early spermatocyte maturation and depletion of spermatids (reduced fertility); meanwhile, absence of AHR in the mammary fat pad leads to overexpression of ERα and enhanced ductal growth. Ahr-/- mouse model, gene expression analysis, histology, serum hormone measurements Proceedings of the National Academy of Sciences of the United States of America Medium 27688768
2017 AHR exerts a cell-cycle regulatory, tumor-suppressive function in pituitary cells independent of exogenous ligand: AHR overexpression in GH3 cells reduced E2F-driven transcription, altered cell cycle regulator gene expression, and increased G0/G1 fraction; co-immunoprecipitation confirmed AHR–retinoblastoma protein (Rb1) interaction as the functional mechanism. AHR overexpression, siRNA knockdown, co-immunoprecipitation (AHR–Rb1), cell cycle analysis, qPCR Endocrine-related cancer Medium 28649092
2021 AHR is activated by coronavirus infection (including SARS-CoV-2); pharmacological inhibition of AHR suppressed HCoV-229E and SARS-CoV-2 replication in vitro, and single-cell RNA-seq from COVID-19 patients detected increased AHR and AHR target gene expression in infected lung epithelial cells. In vitro viral replication assay with AHR inhibitors, single-cell RNA-seq analysis of patient lung tissue Nature communications Medium 34446714
2021 AHR is required for AFB1 (aflatoxin B1) toxicity in hepatocytes: AHR-deficient cells tolerated high AFB1 concentrations with significantly decreased AFB1-DNA adduct formation; AFB1 directly binds the N-terminus of AHR triggering nuclear translocation; AHR mediates P450 enzyme expression induced by AFB1. Genome-wide CRISPR-Cas9 screen, AHR-knockout cell lines, AFB1-DNA adduct quantification, nuclear translocation assay Signal transduction and targeted therapy Medium 34373448
2023 In lung endothelial cells, AHR is highly active and protects against influenza-induced vascular leakage by engaging tissue-protective transcriptional networks including the vasoactive apelin-APJ peptide system; endothelial-specific AHR deletion exacerbates lung damage and promotes apoptosis of airway epithelial cells. Endothelial-specific AHR conditional knockout mouse model, lung permeability assays, influenza infection, transcriptomic analysis Nature High 37587341
2023 AHR acts as a critical node for endothelial sensing of dietary metabolites in the intestine; AHR-mediated signaling in endothelial cells promotes cellular quiescence, vascular normalcy, and restrains inflammatory responses; endothelial AHR deficiency results in dysregulated inflammatory responses and initiation of proliferative pathways; endothelial AHR sensing of dietary ligands is required for protection against enteric infection. Single-cell endothelial atlas, endothelial-specific AHR conditional knockout, transcriptomic analysis, infection challenge Nature High 37586410
2022 UVB-generated DNA damage activates AHR, which cooperates with SP1 to induce MMP2 and MMP11 expression (but not MMP1/3) in keratinocytes; topical AHR antagonists (vitamin B12 and folic acid) ameliorate UVB-induced wrinkle formation in mice while reducing MMP2 expression. Mechanistic studies in HaCaT keratinocytes with AHR/SP1 pathway inhibition/knockdown, reporter assays, mouse wrinkle model with topical antagonists JCI insight Medium 35316219
2019 Homozygous stop-gain mutation (p.Q621*) in AHR causes autosomal recessive foveal hypoplasia and infantile nystagmus in humans; AHR loss-of-function in Ahr-/- mice impairs optic nerve myelin sheath formation and produces conjugate horizontal pendular nystagmus, identifying AHR as a physiological regulator of myelination. Whole exome sequencing (human), Ahr-/- mouse model, optic nerve histology Brain : a journal of neurology High 31009037
2017 AHR deficiency in mice leads to demyelinating disease: Ahr-/- optic nerves show altered lipid composition of the myelin sheath and decreased expression of myelin-associated glycoprotein (MAG), accompanied by increased pro-inflammatory cytokines; inflammation is causally linked to AHR-dependent decreased MAG expression. Ahr-/- mouse model, lipid analysis, immunostaining for MAG, cytokine expression profiling Scientific reports Medium 28851966
2008 cAMP-dependent protein kinase (PKA) can render AHR nuclear and activate AHR-sensitive genes through a mechanism fundamentally different from exogenous ligand-driven nuclear entry, indicating a ligand-independent mode of AHR activation. PKA activation/inhibition studies, nuclear import assays Biochemical pharmacology Low 19013136
2023 Tryptophan deprivation sensitizes the AHR pathway by inducing AHR overexpression (independent of kynurenine but triggered by tryptophan depletion itself) and by increasing cellular kynurenine uptake via GCN2-dependent upregulation of the transporter LAT1 (SLC7A5), so that normally weak AHR agonists such as kynurenine potently activate AHR target genes and potentiate Treg differentiation. RT-qPCR, western blot, Ahr allele variant mouse T cells, Ahr knockout T cells, in vitro Treg differentiation assay Journal for immunotherapy of cancer Medium 37344101
2024 In MerTK+ tumor-associated macrophages, AHR transcriptionally induces ALKAL1, which facilitates MerTK phosphorylation, resulting in heightened phagocytic activity and polarization toward an immunosuppressive phenotype; targeted delivery of an AHR antagonist to tumor-associated macrophages suppressed MerTK expression and improved anti-PD-L1 therapy efficacy. scRNA-seq, mechanistic studies with AHR antagonist, adoptive macrophage transfer, targeted nanoparticle delivery in vivo Science advances Medium 39365866

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Functional role of AhR in the expression of toxic effects by TCDD. Biochimica et biophysica acta 580 12573486
2017 Feedback control of AHR signalling regulates intestinal immunity. Nature 451 28146477
2020 IL4I1 Is a Metabolic Immune Checkpoint that Activates the AHR and Promotes Tumor Progression. Cell 449 32818467
2018 AhR signaling pathways and regulatory functions. Biochimie open 444 30003042
2021 AHR in the intestinal microenvironment: safeguarding barrier function. Nature reviews. Gastroenterology & hepatology 319 33742166
2019 Tryptophan (Trp) modulates gut homeostasis via aryl hydrocarbon receptor (AhR). Critical reviews in food science and nutrition 248 30924357
2018 The Role of the Aryl Hydrocarbon Receptor (AHR) in Immune and Inflammatory Diseases. International journal of molecular sciences 242 30513921
2020 The Aryl Hydrocarbon Receptor (AHR) as a Potential Target for the Control of Intestinal Inflammation: Insights from an Immune and Bacteria Sensor Receptor. Clinical reviews in allergy & immunology 211 32279195
2010 The aryl hydrocarbon receptor (AhR) in the regulation of cell-cell contact and tumor growth. Carcinogenesis 188 20106901
2001 Induction of CYP1A1. The AhR/DRE paradigm: transcription, receptor regulation, and expanding biological roles. Current drug metabolism 182 11469723
2008 AHR-mediated immunomodulation: the role of altered gene transcription. Biochemical pharmacology 149 19100241
2022 Functions of the aryl hydrocarbon receptor (AHR) beyond the canonical AHR/ARNT signaling pathway. Biochemical pharmacology 141 36528068
2013 AhR signalling and dioxin toxicity. Toxicology letters 140 24239782
2008 Growth factors, cytokines and their receptors as downstream targets of arylhydrocarbon receptor (AhR) signaling pathways. Biochemical pharmacology 137 18848820
2014 Role of AhR/ARNT system in skin homeostasis. Archives of dermatological research 130 24966027
2008 AhR acts as an E3 ubiquitin ligase to modulate steroid receptor functions. Biochemical pharmacology 130 18838062
2008 Regulation of constitutive and inducible AHR signaling: complex interactions involving the AHR repressor. Biochemical pharmacology 127 18848529
2000 Binding of aryl hydrocarbon receptor (AhR) to AhR-interacting protein. The role of hsp90. The Journal of biological chemistry 127 10961990
2009 AhR and ARNT modulate ER signaling. Toxicology 121 19778576
2015 AHR Function in Lymphocytes: Emerging Concepts. Trends in immunology 120 26700314
2000 Is CYP1A1 induction always related to AHR signaling pathway? Toxicology 118 11090948
2022 UVB-mediated DNA damage induces matrix metalloproteinases to promote photoaging in an AhR- and SP1-dependent manner. JCI insight 111 35316219
2020 Aryl Hydrocarbon Receptor (AHR) Ligands as Selective AHR Modulators (SAhRMs). International journal of molecular sciences 111 32932962
2023 Activation of aryl hydrocarbon receptor (AhR) in Alzheimer's disease: role of tryptophan metabolites generated by gut host-microbiota. Journal of molecular medicine (Berlin, Germany) 103 36757399
2017 Role of AHR and HIF-1α in Glioblastoma Metabolism. Trends in endocrinology and metabolism: TEM 100 28318896
2012 The AhR twist: ligand-dependent AhR signaling and pharmaco-toxicological implications. Drug discovery today 100 23220635
2008 Timing is everything: consequences of transient and sustained AhR activity. Biochemical pharmacology 98 19027718
2021 AHR mediates the aflatoxin B1 toxicity associated with hepatocellular carcinoma. Signal transduction and targeted therapy 96 34373448
2011 The function of cytochrome P450 1A1 enzyme (CYP1A1) and aryl hydrocarbon receptor (AhR) in the placenta. Current pharmaceutical biotechnology 96 21342125
2023 Endothelial AHR activity prevents lung barrier disruption in viral infection. Nature 95 37587341
2021 Role of AHR Ligands in Skin Homeostasis and Cutaneous Inflammation. Cells 94 34831399
2014 Intersection of AHR and Wnt signaling in development, health, and disease. International journal of molecular sciences 93 25286307
2023 Tryptophan depletion sensitizes the AHR pathway by increasing AHR expression and GCN2/LAT1-mediated kynurenine uptake, and potentiates induction of regulatory T lymphocytes. Journal for immunotherapy of cancer 91 37344101
2019 Aryl hydrocarbon receptor (AHR): From selected human target genes and crosstalk with transcription factors to multiple AHR functions. Biochemical pharmacology 84 31228464
2008 The aryl hydrocarbon receptor (AhR) pathway as a regulatory pathway for cell adhesion and matrix metabolism. Biochemical pharmacology 82 18940186
2020 How the AHR Became Important in Cancer: The Role of Chronically Active AHR in Cancer Aggression. International journal of molecular sciences 81 33396563
2014 Microbiota control of a tryptophan-AhR pathway in disease tolerance to fungi. European journal of immunology 76 25256754
2013 Role of the aryl hydrocarbon receptor (AhR) in lung inflammation. Seminars in immunopathology 75 23963493
2001 Interactions between aryl hydrocarbon receptor (AhR) and hypoxia signaling pathways. Environmental toxicology and pharmacology 73 11382553
2023 Targeting the aryl hydrocarbon receptor (AhR) with BAY 2416964: a selective small molecule inhibitor for cancer immunotherapy. Journal for immunotherapy of cancer 72 37963637
2021 AHR signaling is induced by infection with coronaviruses. Nature communications 71 34446714
2023 Endothelial sensing of AHR ligands regulates intestinal homeostasis. Nature 70 37586410
2018 From TCDD-mediated toxicity to searches of physiologic AHR functions. Biochemical pharmacology 70 30055148
2021 AhR and Cancer: From Gene Profiling to Targeted Therapy. International journal of molecular sciences 67 33451095
2024 The gut microbiota-aromatic hydrocarbon receptor (AhR) axis mediates the anticolitic effect of polyphenol-rich extracts from Sanghuangporus. iMeta 65 38882491
2020 Aryl hydrocarbon receptor (AHR) functions: Balancing opposing processes including inflammatory reactions. Biochemical pharmacology 63 32535108
2014 Immunological Relevance of the Coevolution of IDO1 and AHR. Frontiers in immunology 63 25368620
2008 AhR protein trafficking and function in the skin. Biochemical pharmacology 62 18983832
2020 AhR and IDO1 in pathogenesis of Covid-19 and the "Systemic AhR Activation Syndrome:" a translational review and therapeutic perspectives. Restorative neurology and neuroscience 58 32597823
2020 How the AHR Became Important in Intestinal Homeostasis-A Diurnal FICZ/AHR/CYP1A1 Feedback Controls Both Immunity and Immunopathology. International journal of molecular sciences 58 32784381
2012 The evolving role of the aryl hydrocarbon receptor (AHR) in the normophysiology of hematopoiesis. Stem cell reviews and reports 58 22628113
2019 The aryl hydrocarbon receptor (AhR) as a breast cancer drug target. Medicinal research reviews 57 31721255
2018 Aryl Hydrocarbon Receptor (AhR) Ligands as Selective AhR Modulators: Genomic Studies. Current opinion in toxicology 57 31453421
2017 AhR-deficiency as a cause of demyelinating disease and inflammation. Scientific reports 57 28851966
2022 AHR is a master regulator of diverse pathways in endogenous metabolism. Scientific reports 54 36198709
2018 Perillaldehyde Inhibits AHR Signaling and Activates NRF2 Antioxidant Pathway in Human Keratinocytes. Oxidative medicine and cellular longevity 52 29643980
2010 Potential health-modulating effects of isoflavones and metabolites via activation of PPAR and AhR. Nutrients 51 22254019
2021 The Landscape of AhR Regulators and Coregulators to Fine-Tune AhR Functions. International journal of molecular sciences 50 33451129
2008 Crosstalk between the AHR signaling pathway and circadian rhythm. Biochemical pharmacology 49 18983986
2007 The intersection between the aryl hydrocarbon receptor (AhR)- and retinoic acid-signaling pathways. Vitamins and hormones 47 17368311
2023 AhR, PXR and CAR: From Xenobiotic Receptors to Metabolic Sensors. Cells 45 38067179
2008 AHR-dependent misregulation of Wnt signaling disrupts tissue regeneration. Biochemical pharmacology 45 18938144
2022 AHR and NRF2 in Skin Homeostasis and Atopic Dermatitis. Antioxidants (Basel, Switzerland) 43 35204110
2009 Relevance of the aryl hydrocarbon receptor (AhR) for clinical toxicology. Clinical toxicology (Philadelphia, Pa.) 43 19640236
2023 Cryo-EM structure of the cytosolic AhR complex. Structure (London, England : 1993) 41 36649707
2022 The Role of the Aryl Hydrocarbon Receptor (AhR) and Its Ligands in Breast Cancer. Cancers 41 36428667
2018 Human AHR functions in vascular tissue: Pro- and anti-inflammatory responses of AHR agonists in atherosclerosis. Biochemical pharmacology 41 30508524
2023 Spermidine protects intestinal mucosal barrier function in mice colitis via the AhR/Nrf2 and AhR/STAT3 signaling pathways. International immunopharmacology 39 37104918
2016 Dysregulation of Notch and ERα signaling in AhR-/- male mice. Proceedings of the National Academy of Sciences of the United States of America 39 27688768
2014 AhR-Mediated, Non-Genomic Modulation of IDO1 Function. Frontiers in immunology 39 25360135
2008 An update on the dietary ligands of the AhR. Expert opinion on drug metabolism & toxicology 37 18950284
2022 The Aryl Hydrocarbon Receptor (AHR): A Novel Therapeutic Target for Pulmonary Diseases? International journal of molecular sciences 36 35163440
2022 Aryl hydrocarbon receptor (AhR) reveals evidence of antagonistic pleiotropy in the regulation of the aging process. Cellular and molecular life sciences : CMLS 36 35987825
2020 The Role of Aryl-Hydrocarbon Receptor (AhR) in Osteoclast Differentiation and Function. Cells 34 33066667
2023 Tumor-Suppressive Functions of the Aryl Hydrocarbon Receptor (AhR) and AhR as a Therapeutic Target in Cancer. Biology 33 37106727
2017 Human and rodent aryl hydrocarbon receptor (AHR): from mediator of dioxin toxicity to physiologic AHR functions and therapeutic options. Biological chemistry 33 27805907
2008 AHR signaling in prostate growth, morphogenesis, and disease. Biochemical pharmacology 33 18977204
2008 Role of cAMP in mediating AHR signaling. Biochemical pharmacology 33 19013136
2005 PPARalpha activation potentiates AhR-induced CYP1A1 expression. Toxicology 33 16137816
2018 Isopsoralen Enhanced Osteogenesis by Targeting AhR/ERα. Molecules (Basel, Switzerland) 32 30314280
2019 Involvement of Ahr Pathway in Toxicity of Aflatoxins and Other Mycotoxins. Frontiers in microbiology 31 31681212
2018 AHR Regulates Metabolic Reprogramming to Promote SIRT1-Dependent Keratinocyte Differentiation. The Journal of investigative dermatology 31 30393078
2024 Wogonin improves colitis by activating the AhR pathway to regulate the plasticity of ILC3/ILC1. Phytomedicine : international journal of phytotherapy and phytopharmacology 30 38518634
2020 Assessing the receptor-mediated activity of PAHs using AhR-, ERα- and PPARγ- CALUX bioassays. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 30 32738369
2019 Homozygous stop mutation in AHR causes autosomal recessive foveal hypoplasia and infantile nystagmus. Brain : a journal of neurology 30 31009037
2014 Aryl hydrocarbon receptor (AhR) agonists increase airway epithelial matrix metalloproteinase activity. Journal of molecular medicine (Berlin, Germany) 28 24469321
2024 6PPDQ induces cardiomyocyte senescence via AhR/ROS-mediated autophagic flux blockage. Environmental pollution (Barking, Essex : 1987) 27 38604309
2021 AHR Regulates NK Cell Migration via ASB2-Mediated Ubiquitination of Filamin A. Frontiers in immunology 27 33717133
2017 Red Clover Aryl Hydrocarbon Receptor (AhR) and Estrogen Receptor (ER) Agonists Enhance Genotoxic Estrogen Metabolism. Chemical research in toxicology 27 28985473
2023 Deciphering the roles of aryl hydrocarbon receptor (AHR) in regulating carcinogenesis. Toxicology 26 37480978
2020 Aryl hydrocarbon receptor (AHR), integrating energy metabolism and microbial or obesity-mediated inflammation. Biochemical pharmacology 26 33227291
2023 Aryl hydrocarbon receptor (AhR) impairs circadian regulation: Impact on the aging process. Ageing research reviews 25 37031728
2017 Aryl hydrocarbon receptor (AHR) is a potential tumour suppressor in pituitary adenomas. Endocrine-related cancer 25 28649092
2024 The role of the AHR in host-pathogen interactions. Nature reviews. Immunology 24 39415055
2022 Gut Microbiota Regulation of AHR Signaling in Liver Disease. Biomolecules 24 36139083
2018 Overexpression of aryl hydrocarbon receptor (AHR) signalling pathway in human meningioma. Journal of neuro-oncology 24 29302888
2018 Therapeutic Agents with AHR Inhibiting and NRF2 Activating Activity for Managing Chloracne. Antioxidants (Basel, Switzerland) 24 30011787
2018 Investigation of Nrf2, AhR and ATF4 Activation in Toxicogenomic Databases. Frontiers in genetics 24 30333853
2024 The influence of AHR on immune and tissue biology. EMBO molecular medicine 23 39242971
2024 MerTK+ macrophages promote melanoma progression and immunotherapy resistance through AhR-ALKAL1 activation. Science advances 23 39365866

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