Affinage

DUOX1

Dual oxidase 1 · UniProt Q9NRD9

Length
1551 aa
Mass
177.2 kDa
Annotated
2026-06-09
53 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DUOX1 is a calcium-dependent NADPH oxidase that generates H2O2 at the apical surface of epithelial cells and serves as a signaling hub that converts diverse stimuli into redox-based control of downstream targets (PMID:32929281, PMID:19144650, PMID:17643428). Its activity depends on calcium acting through EF-hand motifs and is uniquely potentiated among DUOX isoforms by cAMP/PKA-mediated phosphorylation at Ser-955 (PMID:19144650); cryo-EM of the DUOX1-DUOXA1 complex resolves a lipid-mediated NADPH-binding pocket, the electron-transfer path, and an inactive dimer-of-dimers state indicating oligomerization-dependent regulation (PMID:32929281). Functional maturation and apical plasma-membrane delivery require the partner factor DUOXA1, whose N-glycosylation directs correct apical targeting, while non-canonical autophagy (ATG5) further controls DUOX1 trafficking to the apical membrane (PMID:39126279, PMID:28982074, PMID:31428054). DUOX1-derived H2O2 acts largely through reversible cysteine oxidation of signaling proteins: in airway epithelia, ATP/P2Y2-recruited DUOX1 sulfenylates and S-glutathionylates Src, ADAM17, and EGFR at Cys-797 to drive EGFR transactivation, cytoskeletal remodeling, and inflammatory output, and in T cells it inactivates SHP-2 to sustain ZAP-70/Lck-dependent TCR signaling and calcium entry (PMID:20682913, PMID:23349873, PMID:27650496, PMID:24624333). Through these redox circuits DUOX1 amplifies type 2 airway inflammation and EGFR-driven asthma pathology, sustains TGF-β1/Smad3 fibrotic signaling by blocking NEDD4L-mediated phospho-Smad3 degradation, and contributes to macrophage profibrotic activation via oxidative Src activation (PMID:32764116, PMID:27812543, PMID:40986746, PMID:35654836). DUOX1 and DUOX2 also act as NAADP-forming enzymes required for T-cell calcium signaling, and DUOX1 mediates testosterone/GPRC6A-driven H2O2 production controlling hair-cycle progression (PMID:34784249, PMID:42047995). Loss-of-function missense mutations in DUOX1 (p.R1307Q) and DUOXA1 (p.R56W) impair H2O2 generation and can cause congenital hypothyroidism (PMID:31428054).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 2007 High

    Establishing that DUOX1 is genuinely responsible for cellular H2O2 output was required before any signaling role could be assigned; knockdown-with-rescue and differentiation studies pinned H2O2 production to DUOX1 protein.

    Evidence siRNA knockdown with lentiviral re-expression rescue in rat thyroid cells, and DCI-differentiated human fetal alveolar type II cells with apical localization

    PMID:17337509 PMID:17643428

    Open questions at the time
    • Did not resolve how DUOX1 activity is switched on at the molecular level
    • Apical localization mechanism not defined
  2. 2009 High

    Defining the activation logic distinguished DUOX1 from DUOX2 and identified its regulatory inputs: calcium via EF-hands and uniquely cAMP/PKA phosphorylation at Ser-955.

    Evidence Co-expression functional assays with DUOXA1/DUOXA2, forskolin/phorbol stimulation, and site-specific phosphorylation mutagenesis in human thyroid cells

    PMID:19144650

    Open questions at the time
    • Kinase that mediates PKA-independent inputs not mapped
    • Structural basis of EF-hand coupling to catalysis unresolved at the time
  3. 2009 High

    Whether the N-terminal peroxidase-homology domain of DUOX1 carries intrinsic enzymatic activity was tested directly; the isolated human domain neither binds heme nor shows peroxidase or SOD activity, constraining models of H2O2 generation.

    Evidence Baculovirus-expressed recombinant peroxidase domains with heme-binding, peroxidase, and SOD assays

    PMID:19460756

    Open questions at the time
    • Function of the N-terminal domain in the full-length enzyme not established
    • Did not test domain behavior within the assembled complex
  4. 2009 Medium

    The first signaling role connected DUOX1-derived H2O2 to innate airway responses, linking ATP stimulation to ADAM17/EGFR shedding, ERK/NF-κB activation, and IL-8 production.

    Evidence DUOX1 siRNA knockdown with intracellular/extracellular catalase scavenging and pathway inhibitors in airway epithelial cells

    PMID:19386603

    Open questions at the time
    • Direct molecular targets of H2O2 not identified
    • Single-lab pharmacology-dependent readouts
  5. 2010 High

    DUOX1 was shown to be a direct amplifier of TCR signaling, defining a redox positive-feedback loop in T cells via SHP-2 inactivation.

    Evidence DUOX1-IP3R1 Co-IP, siRNA/shRNA knockdown, phosphorylation and calcium-flux analysis in primary human CD4+ T cells

    PMID:20682913

    Open questions at the time
    • Direct sulfenylation site on SHP-2 not mapped
    • Mechanism of DUOX1-IP3R1 coupling unresolved
  6. 2010 High

    Genetic deletion established DUOX1 as the dominant urothelial H2O2 source downstream of TRPV4 calcium signaling, with a bladder pressure-response phenotype.

    Evidence Duox1 knockout mice, H2O2 measurement, TRPV4 activation, and bladder pressure measurements

    PMID:21146788

    Open questions at the time
    • Downstream redox targets in urothelium not identified
    • Physiological signaling output incompletely defined
  7. 2013 High

    The redox mechanism of EGFR transactivation was resolved at the protein level, showing DUOX1 oxidizes cysteines in Src and ADAM17 within a P2Y2-recruited complex.

    Evidence Reciprocal Co-IP, thiol-specific labeling, knockdown, and EGFR phosphorylation/migration assays in airway epithelial cells

    PMID:23349873

    Open questions at the time
    • Specific oxidized cysteines on ADAM17 not pinpointed
    • Kinetics of complex assembly not defined
  8. 2014 High

    Proteome-scale S-glutathionylation mapping defined the breadth of DUOX1 redox targets controlling cytoskeleton and MAPK signaling.

    Evidence Stable shRNA and DUOX1-deficient mouse tracheal cells with biotin-GSH labeling and global proteomics

    PMID:24624333

    Open questions at the time
    • Functional consequence of each glutathionylation event not individually validated
    • Reversal/deglutathionylation kinetics not addressed
  9. 2014 Medium

    A hormone-sensing input was identified, linking testosterone via GPRC6A/Gq/IP3/calcium to DUOX1 H2O2 production in keratinocytes.

    Evidence GPRC6A siRNA knockdown with calcium imaging, IP3 quantification, and H2O2 measurement in a 3D skin model

    PMID:25164816

    Open questions at the time
    • Single-lab siRNA evidence
    • Downstream redox targets in keratinocytes not identified
  10. 2015 High

    DUOX1 was implicated in damage signaling, showing radiation-induced p38/IL-13-sustained DUOX1 expression drives persistent DNA double-strand breaks in thyroid cells.

    Evidence siRNA knockdown with p38 inhibitors and catalase rescue, γH2AX assays, and human thyroid tissue analysis

    PMID:25848056

    Open questions at the time
    • Mechanism by which apical H2O2 reaches nuclear DNA not defined
    • Long-term carcinogenic consequence not established
  11. 2015 Medium

    An ortholog model defined an epigenetic mechanism for DUOX-driven inflammation, linking H2O2 to JNK/AP-1 and histone marks at the cxcl8 promoter.

    Evidence Zebrafish duox1 morpholino knockdown, JNK inhibitors, and ChIP for histone modifications at wounds

    PMID:25582859

    Open questions at the time
    • Conservation of the histone-mark mechanism in mammals not shown
    • Morpholino-based knockdown only
  12. 2016 High

    The activating redox modification of EGFR was pinpointed: sulfenylation (not S-glutathionylation) of Cys-797 is the kinase-activating event.

    Evidence Recombinant kinase assays with H2O2/GSSG, C797S mutagenesis, redox labeling, and DUOX1 knockdown

    PMID:27650496

    Open questions at the time
    • In vivo occupancy of Cys-797 sulfenylation not quantified
    • Reversal mechanism not detailed
  13. 2016 High

    In vivo asthma modeling established DUOX1 as a driver of type 2 airway pathology via sustained EGFR/Src cysteine oxidation.

    Evidence DUOX1-deficient mice and intratracheal siRNA in an HDM model, with EGFR oxidation assays and asthmatic patient cells

    PMID:27812543

    Open questions at the time
    • Relative contribution of epithelial vs other cell types not yet separated
    • Causal cytokine hierarchy incompletely defined
  14. 2016 Medium

    A context-dependent tumor-suppressive role emerged, with DUOX1 loss promoting EMT, stemness, and EGFR-TKI resistance in lung epithelial cells.

    Evidence shRNA knockdown and overexpression with EMT markers, migration, anchorage-independent growth, and xenograft assays

    PMID:27694834

    Open questions at the time
    • Mechanism linking DUOX1 loss to EMT transcriptional program unresolved
    • Single-lab in vitro/xenograft evidence
  15. 2017 Medium

    Trafficking control of DUOX1 was extended to non-canonical autophagy, with ATG5 required for apical membrane localization independent of protein levels.

    Evidence ATG5 and DUOX1 siRNA, confocal localization, EPR superoxide measurement, and OVA mouse model

    PMID:28982074

    Open questions at the time
    • Molecular machinery linking ATG5 to DUOX1 trafficking unknown
    • Single-lab siRNA evidence
  16. 2018 High

    DUOX1 was shown to negatively regulate adaptive immunity, restraining B-cell proliferation downstream of BCR/IL-4.

    Evidence Duox1 knockout mice, BCR stimulation, catalase rescue, and in vivo germinal center analysis

    PMID:30559322

    Open questions at the time
    • Redox targets restraining B-cell proliferation not identified
    • Distinction from antibody-isotype output mechanistically unexplained
  17. 2018 Medium

    An ion-transport regulatory role was defined, with DUOX1 H2O2 acutely activating ENaC while transcriptionally repressing it in a feedback loop.

    Evidence Perforated patch-clamp electrophysiology with catalase/DPI inhibition in H441 bronchiolar cells

    PMID:30052308

    Open questions at the time
    • Direct ENaC redox target site not mapped
    • Single-lab pharmacology-based attribution
  18. 2019 Medium

    Patient-derived mutations established a human disease link and reinforced DUOXA1 dependence, with DUOX1 p.R1307Q and DUOXA1 p.R56W impairing H2O2 generation in congenital hypothyroidism.

    Evidence Patient sequencing with functional H2O2 assays, qRT-PCR, and Western blot in transfected cells

    PMID:31428054

    Open questions at the time
    • Single-lab functional validation
    • Genotype-phenotype penetrance not fully established
  19. 2021 High

    A fibrosis-amplifying mechanism was defined, with DUOX1 H2O2 stabilizing phospho-Smad3 by blocking NEDD4L-mediated ubiquitination.

    Evidence DUOX1-deficient mice, primary lung fibroblasts, pSmad3/NEDD4L Co-IP, and ubiquitination assays

    PMID:32764116

    Open questions at the time
    • Direct redox target controlling pSmad3-NEDD4L interaction not identified
    • Whether effect requires apical vs intracellular H2O2 unresolved
  20. 2021 High

    An unexpected enzymatic activity was demonstrated, with DUOX1/DUOX2 acting as NAADP-forming enzymes required for T-cell calcium signaling.

    Evidence In vitro NAADP-forming enzyme assay and Duox/Duoxa knockout mouse T cells with local and global Ca2+ imaging

    PMID:34784249

    Open questions at the time
    • Relationship between NAADP synthesis and H2O2-generating activity not reconciled
    • Structural basis of NAADP formation not defined
  21. 2022 High

    Cell-type-specific deletion dissected epithelial versus macrophage DUOX1 contributions to chronic allergic airway disease.

    Evidence Conditional epithelial and macrophage DUOX1 knockouts in chronic HDM model with cytokine, mucus, and flow-cytometry readouts

    PMID:35654836

    Open questions at the time
    • Macrophage-intrinsic redox targets not yet defined here
    • Crosstalk signals between compartments not fully mapped
  22. 2024 High

    The apical-targeting mechanism was resolved at the molecular level, showing DUOXA1 N-glycosylation directs DUOX1 to the apical membrane, distinct from DUOXA2's mechanism.

    Evidence MDCK co-expression with N-glycosylation mutants, immunofluorescence localization, and domain-swap experiments

    PMID:39126279

    Open questions at the time
    • Glycan-reading trafficking machinery not identified
    • How glycosylation status is regulated physiologically unknown
  23. 2026 High

    Macrophage-intrinsic DUOX1 was mechanistically tied to profibrotic activation via oxidative Src activation and macrophage-fibroblast crosstalk.

    Evidence LysM-Cre conditional DUOX1 knockout with BMDM migration, cysteine oxidation, collagen, and saracatinib inhibition

    PMID:40986746

    Open questions at the time
    • Oxidized Src cysteine residues in macrophages not pinpointed
    • Therapeutic targetability not established
  24. 2026 Medium

    The testosterone/GPRC6A-DUOX1 axis was extended to an in vivo physiological output, controlling hair-cycle progression and androgenetic hair loss.

    Evidence GPRC6A and Duox1 knockout mice and keratinocytes with H2O2, apoptosis, Ki-67, and hair-cycle staging after topical testosterone

    PMID:42047995

    Open questions at the time
    • Downstream redox effectors in follicle keratinocytes not identified
    • Single-lab mouse evidence

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DUOX1's H2O2-generating and NAADP-forming activities are coordinated, and which specific cysteine targets mediate each tissue-specific outcome, remains unresolved.
  • No unified model reconciling NAADP synthesis with NADPH-oxidase output
  • Tissue-specific redox-target catalogs incomplete
  • Regulation of inactive dimer-of-dimers state in vivo not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0016491 oxidoreductase activity 3 GO:0016740 transferase activity 1 GO:0140657 ATP-dependent activity 1
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 4 R-HSA-8953897 Cellular responses to stimuli 2
Partners
ADAM17DUOXA1EGFRIP3R1NEDD4LP2Y2SHP-2SRC
Complex memberships
DUOX1-DUOXA1 complex

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2020 Cryo-EM structures of mouse DUOX1-DUOXA1 complex (with and without NADPH substrate) reveal atomic details of DUOX1-DUOXA1 interaction, a lipid-mediated NADPH-binding pocket, and the electron transfer path. A dimer-of-dimers configuration was identified as an inactive state, suggesting an oligomerization-dependent regulatory mechanism. Cryo-EM structural determination, biochemical assays Nature structural & molecular biology High 32929281
2009 DUOX1 activity depends on calcium and functional EF-hand motifs. Uniquely among DUOX isoforms, DUOX1 (but not DUOX2) activity is stimulated by cAMP/forskolin via PKA-mediated phosphorylation on serine 955. This differential regulation was confirmed in human thyroid cells co-expressing DUOX1 with its maturation factor DUOXA1. Co-expression functional assay with DuoxA1/DuoxA2, pharmacological stimulation (forskolin, phorbol esters), site-specific mutagenesis of phosphorylation sites, membrane expression analysis The Journal of biological chemistry High 19144650
2009 The isolated human DUOX1 peroxidase domain (hDUOX1 aa 1–593) does not bind heme and has no intrinsic peroxidase activity, in contrast to the C. elegans ortholog. Neither DUOX1 domain showed significant superoxide dismutase activity, suggesting the N-terminal motif does not directly convert superoxide to H2O2 in isolation. Baculovirus expression and purification of recombinant peroxidase domains, heme-binding assays, peroxidase activity assays, superoxide dismutase activity assays The Journal of biological chemistry High 19460756
2010 DUOX1 binds to inositol 1,4,5-trisphosphate receptor 1 (IP3R1) in primary human CD4+ T cells and is required for early TCR-stimulated H2O2 production. DUOX1-derived H2O2 inactivates SHP-2 phosphatase, promoting ZAP-70 phosphorylation at Tyr-319 and its association with Lck and CD3ζ, thereby creating a positive feedback loop that sustains TCR signaling, store-operated Ca2+ entry, and ERK activation. Co-immunoprecipitation (DUOX1-IP3R1), siRNA/shRNA knockdown, TCR signaling assays, phosphorylation analysis, calcium flux measurement, cytokine production assays Science signaling High 20682913
2013 ATP activates DUOX1 via purinergic P2Y2 receptor stimulation, recruiting Src and DUOX1 into a signaling complex. DUOX1-derived H2O2 oxidizes cysteine residues within Src and ADAM17, activating both; ADAM17 then sheds EGFR ligands, leading to EGFR transactivation and downstream wound responses in airway epithelial cells. siRNA/shRNA knockdown, thiol-specific biotin labeling for cysteine oxidation detection, Co-IP (P2Y2R/Src/DUOX1 complex), EGFR phosphorylation assays, cell migration assays PloS one High 23349873
2016 ATP-dependent EGFR transactivation in airway epithelial cells involves DUOX1-dependent sequential sulfenylation and S-glutathionylation of cysteine residues within EGFR and Src. The intermediate sulfenylation (not S-glutathionylation) is the activating modification; C797S EGFR variant abolishes H2O2-induced EGFR kinase activation, identifying Cys-797 as the redox-sensitive regulatory site. Recombinant protein kinase activity assays with H2O2/GSSG, C797S mutagenesis, redox-labeling strategies, DUOX1 siRNA/shRNA knockdown The Journal of biological chemistry High 27650496
2014 DUOX1 mediates ATP-stimulated transient H2O2 production and S-glutathionylation of multiple proteins in airway epithelial cells, including β-actin, peroxiredoxin 1, Src, and MAPK phosphatase 1. These DUOX1-dependent S-glutathionylation events regulate cytoskeletal dynamics and MAPK signaling involved in cell migration. Stable shRNA knockdown, primary tracheal epithelial cells from DUOX1-deficient mice, biotin-tagged GSH labeling, avidin purification, global proteomics, H2O2 measurement Redox biology High 24624333
2009 ATP-mediated DUOX1 activation in airway epithelial cells leads to H2O2-dependent activation of ERK1/2 and NF-κB pathways, intracellular oxidant signaling, and EGFR ligand shedding by ADAM17, culminating in IL-8/CXCL8 production in response to bacterial stimuli. DUOX1 siRNA knockdown, catalase (extracellular and intracellular scavenging), ERK/NF-κB pathway inhibitors, ADAM17 activation assays, IL-8 ELISA The Journal of biological chemistry Medium 19386603
2015 Ionizing radiation induces DUOX1-dependent H2O2 production in thyroid cells via a pathway involving p38 MAPK activation and IL-13 upregulation, which in turn sustains DUOX1 expression for days after irradiation. DUOX1-derived H2O2 causes persistent DNA double-strand breaks; catalase pretreatment or DUOX1 siRNA knockdown abrogates this damage. siRNA knockdown, p38 MAPK inhibitors, catalase treatment, DNA damage assays (γH2AX), dose-response H2O2 measurement, human thyroid tissue analysis Proceedings of the National Academy of Sciences of the United States of America High 25848056
2021 DUOX1-derived H2O2 sustains TGF-β1/Smad3 signaling in lung fibroblasts by preventing phospho-Smad3 degradation. Mechanistically, DUOX1 inhibits the interaction between phospho-Smad3 and the ubiquitin ligase NEDD4L, thereby preventing NEDD4L-mediated ubiquitination and proteasomal degradation of phospho-Smad3. DUOX1-deficient mouse models, primary human/mouse lung fibroblasts, Co-IP (pSmad3/NEDD4L interaction), ubiquitination assays, Smad3 phosphorylation kinetics The European respiratory journal High 32764116
2016 DUOX1 mediates persistent EGFR activation and cysteine oxidation within EGFR and Src in airway epithelial cells during allergic asthma. DUOX1 deficiency attenuated HDM-induced mucous metaplasia, subepithelial fibrosis, neutrophilic inflammation, type 2 cytokine production (IL-33, IL-13), and central airway resistance in mice. DUOX1-deficient mice, HDM mouse model, siRNA intratracheal delivery, EGFR cysteine oxidation assays, nasal epithelial cells from asthmatic subjects, EGFR/Src phosphorylation analysis JCI insight High 27812543
2010 DUOX1 is the main source of H2O2 in urothelial cells, as demonstrated using Duox1 knockout mice. TRPV4 calcium channel activation elicits a calcium signal that stimulates DUOX1-dependent H2O2 production, and Duox1 knockout animals display altered pressure responses in the urinary bladder. Duox1 gene-deficient mouse model, H2O2 measurement, TRPV4 pharmacological activation, bladder pressure measurements Free radical biology & medicine High 21146788
2007 Duox1 is the main source of H2O2 in the rat thyroid cell line PCCl3, as demonstrated by siRNA knockdown reducing H2O2 production in parallel with Duox1 protein. Re-expression of rat Duox1 fully rescued H2O2 production, while human Duox1 partial rescue was also observed. siRNA knockdown, lentiviral re-expression rescue, H2O2 production assays, Western blot Experimental cell research High 17643428
2024 DUOX1 is sorted to the apical plasma membrane in epithelial cells via its maturation factor DUOXA1. N-glycosylation of DUOXA1 is required for apical targeting of DUOX1; impairment of DUOXA1 N-glycosylation results in DUOX1 mistargeting to the basolateral membrane. DUOX2 apical sorting by DUOXA2 is regulated by a distinct mechanism involving DUOXA2's C-terminal region rather than N-glycosylation. MDCK epithelial cell co-expression system, N-glycosylation mutants of DUOXA1/DUOXA2, immunofluorescence localization, domain-swap experiments Genes to cells High 39126279
2021 DUOX1 and DUOX2 function as NAADP-forming enzymes that convert NAADPH to NAADP in vitro under physiological conditions. In T cells, DUOX1 and DUOX2 are required for global Ca2+ signaling (4–12 min post-stimulation), while DUOX2 specifically drives early Ca2+ microdomain formation (first 15 s). Duoxa1/Duoxa2 double KO but not single Nox1 or Nox2 KO reduced local and global Ca2+ signaling. In vitro NAADP-forming enzyme assay, Duox1/Duox2/Duoxa1/Duoxa2 knockout mouse T cells, Ca2+ imaging (local microdomains and global), genetic epistasis with single and double KOs Science signaling High 34784249
2014 Testosterone activates Duox1 in epidermal keratinocytes through GPRC6A, a membrane receptor that senses testosterone and activates Gq protein, leading to IP3 generation, intracellular calcium mobilization, and subsequent Duox1-dependent H2O2 generation. GPRC6A silencing abolished testosterone-induced calcium and H2O2 responses. GPRC6A siRNA knockdown, calcium imaging, H2O2 measurement, IP3 quantification, caspase-3 activation assays, 3D skin equivalent model The Journal of biological chemistry Medium 25164816
2017 Autophagy protein ATG5 is required for apical membrane localization of DUOX1 in airway epithelial cells during chronic IL-13 stimulation. ATG5 depletion significantly reduced intracellular superoxide production without diminishing total DUOX1 protein levels, indicating that non-canonical autophagy regulates DUOX1 trafficking to the apical membrane rather than its expression. ATG5 siRNA, DUOX1 siRNA, confocal immunofluorescence localization, electron paramagnetic resonance spectroscopy for superoxide, OVA mouse model, LC3BII Western blot Redox biology Medium 28982074
2018 Duox1-derived H2O2 negatively regulates proliferative activity (but not Ig isotype production) in primary splenic B cells upon BCR stimulation. IL-4 costimulation boosts Duox1 expression and H2O2 production; Duox1-/- CD19+ B cells show enhanced proliferation, and catalase treatment of WT B cells mimics this effect. Immunized Duox1-/- mice show increased B cell expansion in germinal centers. Duox1 knockout mice, BCR stimulation assays, H2O2 measurement, proliferation assays, catalase treatment, in vivo immunization, germinal center analysis Journal of immunology High 30559322
2015 Duox1-derived H2O2 promotes late-phase neutrophil recruitment to wounds in zebrafish by inducing Cxcl8 expression via JNK/c-JUN/AP-1 signaling. This H2O2-driven cxcl8 induction is accompanied by histone modifications (increased H3K4me3, H3K9ac; decreased H3K9me3) at the cxcl8 promoter. ERK and NF-κB signaling were not involved. Zebrafish duox1 morpholino knockdown, wound assays, JNK inhibitors, ChIP for histone modifications, neutrophil recruitment quantification Journal of immunology Medium 25582859
2019 DUOX1 missense mutation p.R1307Q impairs H2O2 generation and reduces DUOX1 mRNA and protein expression. A companion DUOXA1 mutation p.R56W similarly reduces DUOX1 expression and H2O2 generation, demonstrating that intact DUOXA1 is required for full DUOX1 activity; both mutations can cause congenital hypothyroidism. Patient sequencing, functional H2O2 generation assays in transfected cells, qRT-PCR, Western blot Frontiers in endocrinology Medium 31428054
2016 Loss of DUOX1 expression in lung epithelial cells promotes epithelial-to-mesenchymal transition (EMT), characterized by loss of E-cadherin, gain of vimentin/collagen, increased migration, anchorage-independent growth, and enhanced cancer stem cell markers (CD133, ALDH1). Conversely, overexpression of DUOX1 in A549 cells reverses EMT features, and DUOX1 loss confers resistance to EGFR tyrosine kinase inhibitors. shRNA stable knockdown, DUOX1 overexpression, E-cadherin/vimentin Western blot, migration assays, anchorage-independent growth, in vivo xenograft invasion assay, erlotinib resistance assays Oncogenesis Medium 27694834
2026 DUOX1 in macrophages contributes to profibrotic activation through oxidative activation of Src kinase via cysteine oxidation. Myeloid-specific conditional DUOX1 deletion attenuated pulmonary fibrosis, impaired MoMac recruitment, reduced collagen production, and improved oxygen saturation. DUOX1 also contributes to in vitro macrophage migration and EGFR ligand production involved in macrophage-fibroblast cross-talk. LysM-Cre conditional DUOX1 knockout, BMDM migration assays, cysteine oxidation assays, collagen production measurement, Src kinase activation assays, saracatinib pharmacological inhibition American journal of respiratory cell and molecular biology High 40986746
2026 The GPRC6A-Duox1 axis regulates hair cycle progression downstream of testosterone signaling. GPRC6A-deficient and Duox1-deficient keratinocytes fail to generate H2O2 in response to testosterone. Both GPRC6A KO and Duox1 KO mice show extended anagen phase, increased Ki-67 expression, longer hair, and resistance to testosterone-mediated hair loss. GPRC6A and Duox1 knockout mice and keratinocytes, H2O2 measurement, apoptosis assays, Ki-67 immunostaining, hair cycle staging, topical testosterone application Tissue engineering and regenerative medicine Medium 42047995
2018 DUOX1-derived H2O2 regulates sodium transport (ENaC activity) in H441 bronchiolar epithelial cells. Dexamethasone-induced dome formation is inhibited by extracellular catalase or NADPH oxidase inhibitor DPI. H2O2 (0.2 mmol/L) acutely activates amiloride-sensitive ENaC currents in dome-forming cells, and there is a negative feedback loop where H2O2 inhibits ENaC gene transcription. Nystatin-perforated patch-clamp electrophysiology, catalase treatment, DPI inhibition, DUOX1 immunocytochemistry, RT-PCR, dome formation assays Acta physiologica Medium 30052308
2022 Macrophage-intrinsic DUOX1 contributes to type 2 inflammation and mucus metaplasia during chronic HDM-driven allergic airway disease. Cell-type-specific conditional deletion revealed that epithelial DUOX1 drives acute HDM responses and most features of chronic inflammation, while macrophage DUOX1 additionally contributes to macrophage recruitment, type 2 cytokine production, and mucus metaplasia. Conditional cell-type-specific DUOX1 knockout (epithelial and macrophage lineages), HDM mouse model, cytokine measurement, mucus staining, flow cytometry Mucosal immunology High 35654836
2007 DUOX1 expression and its maturation factor DUOXA1 are co-upregulated during differentiation of human fetal lung cells into alveolar type II cells (induced by DCI treatment), with DUOX1 protein localizing near the apical cell pole. DUOX1 knockdown by siRNA blocked increases in H2O2 production and acid secretion in differentiated type II cells, establishing DUOX1 as responsible for alveolar H2O2 and acid production. Human fetal lung primary cell culture, DCI differentiation protocol, siRNA knockdown, H2O2 measurement, intracellular acid measurement, immunofluorescence localization American journal of physiology. Lung cellular and molecular physiology Medium 17337509
2023 HIF-2α transcriptionally promotes DUOX1 expression (confirmed by dual luciferase assay), and arsenic-induced upregulation of DUOX1 suppresses GPX4 expression, promoting ferroptosis in kidney cells. DUOX1 siRNA knockdown significantly upregulated GPX4 and attenuated ferroptosis. siRNA knockdown, dual luciferase reporter assay for HIF-2α binding to DUOX1 promoter, GPX4 Western blot, ferroptosis markers, in vivo arsenic exposure model The Science of the total environment Medium 37879473

Source papers

Stage 0 corpus · 53 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Differential regulation of dual NADPH oxidases/peroxidases, Duox1 and Duox2, by Th1 and Th2 cytokines in respiratory tract epithelium. FEBS letters 195 16111680
2009 Activation of dual oxidases Duox1 and Duox2: differential regulation mediated by camp-dependent protein kinase and protein kinase C-dependent phosphorylation. The Journal of biological chemistry 176 19144650
2009 Ce-Duox1/BLI-3 generates reactive oxygen species as a protective innate immune mechanism in Caenorhabditis elegans. Infection and immunity 118 19687201
2010 The nonphagocytic NADPH oxidase Duox1 mediates a positive feedback loop during T cell receptor signaling. Science signaling 112 20682913
2015 NADPH oxidase DUOX1 promotes long-term persistence of oxidative stress after an exposure to irradiation. Proceedings of the National Academy of Sciences of the United States of America 107 25848056
2009 ATP-mediated activation of the NADPH oxidase DUOX1 mediates airway epithelial responses to bacterial stimuli. The Journal of biological chemistry 80 19386603
2010 Urothelial cells produce hydrogen peroxide through the activation of Duox1. Free radical biology & medicine 79 21146788
2009 Caenorhabditis elegans and human dual oxidase 1 (DUOX1) "peroxidase" domains: insights into heme binding and catalytic activity. The Journal of biological chemistry 67 19460756
2016 DUOX1 mediates persistent epithelial EGFR activation, mucous cell metaplasia, and airway remodeling during allergic asthma. JCI insight 62 27812543
2013 ATP-mediated transactivation of the epidermal growth factor receptor in airway epithelial cells involves DUOX1-dependent oxidation of Src and ADAM17. PloS one 60 23349873
2007 Developmental regulation of DUOX1 expression and function in human fetal lung epithelial cells. American journal of physiology. Lung cellular and molecular physiology 59 17337509
2017 Digenic DUOX1 and DUOX2 Mutations in Cases With Congenital Hypothyroidism. The Journal of clinical endocrinology and metabolism 53 28633507
2016 DUOX1 silencing in lung cancer promotes EMT, cancer stem cell characteristics and invasive properties. Oncogenesis 52 27694834
2021 NADPH oxidase DUOX1 sustains TGF-β1 signalling and promotes lung fibrosis. The European respiratory journal 51 32764116
2016 The NADPH Oxidases DUOX1 and NOX2 Play Distinct Roles in Redox Regulation of Epidermal Growth Factor Receptor Signaling. The Journal of biological chemistry 50 27650496
2017 Autophagy regulates DUOX1 localization and superoxide production in airway epithelial cells during chronic IL-13 stimulation. Redox biology 45 28982074
2021 Dual NADPH oxidases DUOX1 and DUOX2 synthesize NAADP and are necessary for Ca2+ signaling during T cell activation. Science signaling 44 34784249
2015 Duox1-derived H2O2 modulates Cxcl8 expression and neutrophil recruitment via JNK/c-JUN/AP-1 signaling and chromatin modifications. Journal of immunology (Baltimore, Md. : 1950) 37 25582859
2014 Testosterone stimulates Duox1 activity through GPRC6A in skin keratinocytes. The Journal of biological chemistry 33 25164816
2012 Reactive oxygen species regulate the levels of dual oxidase (Duox1-2) in human neuroblastoma cells. PloS one 33 22523549
2020 Structures of mouse DUOX1-DUOXA1 provide mechanistic insights into enzyme activation and regulation. Nature structural & molecular biology 32 32929281
2019 Melatonin Attenuates Upregulation of Duox1 and Duox2 and Protects against Lung Injury following Chest Irradiation in Rats. Cell journal 31 31210428
2016 Nox4 and Duox1/2 Mediate Redox Activation of Mesenchymal Cell Migration by PDGF. PloS one 26 27110716
2014 Identification of DUOX1-dependent redox signaling through protein S-glutathionylation in airway epithelial cells. Redox biology 25 24624333
2013 P. aeruginosa lipopolysaccharide-induced MUC5AC and CLCA3 expression is partly through Duox1 in vitro and in vivo. PloS one 25 23691121
2011 NADPH oxidase DUOX1 and DUOX2 but not NOX4 are independent predictors in hepatocellular carcinoma after hepatectomy. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 25 21915726
2017 Cigarette Smoke Impairs A2A Adenosine Receptor Mediated Wound Repair through Up-regulation of Duox-1 Expression. Scientific reports 24 28337995
2007 Duox1 is the main source of hydrogen peroxide in the rat thyroid cell line PCCl3. Experimental cell research 22 17643428
2023 Salvianolic acid A attenuates arsenic-induced ferroptosis and kidney injury via HIF-2α/DUOX1/GPX4 and iron homeostasis. The Science of the total environment 21 37879473
2016 Overexpression of Interleukin-4 in the Thyroid of Transgenic Mice Upregulates the Expression of Duox1 and the Anion Transporter Pendrin. Thyroid : official journal of the American Thyroid Association 19 27599561
2021 DUOX1 in mammalian disease pathophysiology. Journal of molecular medicine (Berlin, Germany) 17 33704512
2023 ZC3H13 reduced DUOX1-mediated ferroptosis in laryngeal squamous cell carcinoma cells through m6A-dependent modification. Tissue & cell 16 37536262
2019 Identification of Two Missense Mutations in DUOX1 (p.R1307Q) and DUOXA1 (p.R56W) That Can Cause Congenital Hypothyroidism Through Impairing H2O2 Generation. Frontiers in endocrinology 16 31428054
2016 Acrolein and thiol-reactive electrophiles suppress allergen-induced innate airway epithelial responses by inhibition of DUOX1 and EGFR. American journal of physiology. Lung cellular and molecular physiology 15 27612966
2021 Downregulation of epithelial DUOX1 in chronic obstructive pulmonary disease. JCI insight 13 33301419
2022 Macrophage-intrinsic DUOX1 contributes to type 2 inflammation and mucus metaplasia during allergic airway disease. Mucosal immunology 11 35654836
2018 DUOX1 Silencing in Mammary Cell Alters the Response to Genotoxic Stress. Oxidative medicine and cellular longevity 11 29849884
2018 Duox1 Regulates Primary B Cell Function under the Influence of IL-4 through BCR-Mediated Generation of Hydrogen Peroxide. Journal of immunology (Baltimore, Md. : 1950) 8 30559322
2024 The NADPH oxidases DUOX1 and DUOX2 are sorted to the apical plasma membrane in epithelial cells via their respective maturation factors DUOXA1 and DUOXA2. Genes to cells : devoted to molecular & cellular mechanisms 7 39126279
2023 Diet-induced obesity worsens allergen-induced type 2/type 17 inflammation in airways by enhancing DUOX1 activation. American journal of physiology. Lung cellular and molecular physiology 5 36625485
2021 Knockdown of Dual Oxidase 1 (DUOX1) Promotes Wound Healing by Regulating Reactive Oxygen Species (ROS) by Activation of Nuclear Kactor kappa B (NF-κB) Signaling. Medical science monitor : international medical journal of experimental and clinical research 5 33563887
2020 Vitamin D Attenuates Hypoxia-Induced Injury in Rat Primary Neuron Cells through Downregulation of the Dual Oxidase 1 (DUOX1) Gene. Medical science monitor : international medical journal of experimental and clinical research 4 32712621
2025 Geniposide Suppresses Tumor Progression Through DUOX1-Mediated Ferroptosis in Hepatocellular Carcinoma. The American journal of Chinese medicine 3 40621626
2015 Site-specific Effects of DUOX1-Related Peroxidase on Intercellular Apoptosis Signaling. Anticancer research 3 26504019
2025 Eosinophil-airway epithelial cell crosstalk reveals the eosinophil-mediated DUOX1 upregulation in a murine allergic inflammation setting. Journal of leukocyte biology 2 39447011
2025 DUOX1 inhibits the progression of rheumatoid arthritis by regulating the NF-κB pathway in vitro. Allergologia et immunopathologia 2 40088033
2023 DUOX1 Gene Missense Mutation Confers Susceptibility on Type 2 Amiodarone-Induced Thyrotoxicosis. International journal of molecular sciences 2 36835420
2023 Dual Role of DUOX1-Derived Reactive Oxygen Species in Melanoma. Antioxidants (Basel, Switzerland) 2 36978957
2018 Functional Annotation and Analysis of Dual Oxidase 1 (DUOX1): a Potential Anti-pyocyanin Immune Component. Interdisciplinary sciences, computational life sciences 2 30483939
2018 DUOX1-mediated hydrogen peroxide release regulates sodium transport in H441 bronchiolar epithelial cells. Acta physiologica (Oxford, England) 1 30052308
2026 The NADPH oxidase DUOX1 contributes to profibrotic macrophage activation and pulmonary fibrosis. American journal of respiratory cell and molecular biology 0 40986746
2026 Corrigendum to: DUOX1 inhibits the progression of rheumatoid arthritis by regulating the NF-κB pathway in vitro. Allergologia et immunopathologia 0 41910349
2026 GPRC6A-Duox1 Axis Regulates the Hair Cycle Through H2O2 Generation. Tissue engineering and regenerative medicine 0 42047995

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