Affinage

DUOX1

Dual oxidase 1 · UniProt Q9NRD9

Length
1551 aa
Mass
177.2 kDa
Annotated
2026-04-28
52 papers in source corpus 27 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DUOX1 is a calcium-dependent NADPH oxidase that generates H₂O₂ at epithelial surfaces and in immune cells, coupling receptor-mediated calcium signals to redox-dependent signaling cascades that regulate innate defense, tissue remodeling, and lymphocyte activation. Functional DUOX1 requires co-assembly with its maturation factor DUOXA1, whose N-glycosylation directs apical membrane sorting; the complex forms a dimer-of-dimers architecture with a lipid-mediated NADPH-binding pocket and defined electron transfer path, and its activity is positively regulated by EF-hand calcium binding and PKA phosphorylation at Ser955 (PMID:19144650, PMID:32929281, PMID:39126279). DUOX1-derived H₂O₂ activates downstream signaling through cysteine oxidation of specific targets—sulfenylation of Src and EGFR Cys-797 drives EGFR transactivation and ADAM17-mediated ligand shedding, oxidative inactivation of SHP-2 amplifies TCR/ZAP-70 signaling, and inhibition of NEDD4L–phospho-Smad3 interaction sustains TGF-β/Smad3 signaling (PMID:27650496, PMID:20682913, PMID:23349873, PMID:32764116). Beyond epithelial defense, DUOX1 synthesizes NAADP to support global Ca²⁺ signaling during T cell activation, negatively regulates B cell proliferation, and drives profibrotic macrophage activation through Src oxidation in pulmonary fibrosis (PMID:34784249, PMID:30559322, PMID:40986746).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 2007 High

    Establishing that DUOX1 is the dominant H₂O₂ source in thyroid cells resolved which NOX family member fulfills this function, while parallel work showed DUOX1 is developmentally regulated and apically localized in lung epithelial cells.

    Evidence siRNA knockdown with re-expression rescue in PCCl3 thyroid cells; siRNA KD in differentiating fetal lung alveolar type II cells with immunofluorescence localization

    PMID:17337509 PMID:17643428

    Open questions at the time
    • Mechanism of DUOX1 activation and co-factor requirements not yet defined
    • Species-specific differences in rescue efficiency unexplained
  2. 2009 High

    Defining the regulatory logic of DUOX1 activation—calcium/EF-hand dependence, PKA/Ser955 phosphorylation, and obligate DUOXA1 co-expression—established the enzymatic control architecture and resolved how DUOX1 differs from DUOX2 (PKC-regulated).

    Evidence Site-directed mutagenesis of EF-hand motifs, phosphorylation mapping, forskolin stimulation, co-expression with DUOXA1 in reconstituted systems and primary thyroid cells

    PMID:19144650

    Open questions at the time
    • Structural basis of DUOXA1 requirement unknown
    • Downstream signaling targets of DUOX1-derived H₂O₂ not identified
  3. 2009 High

    Demonstrating that the human DUOX1 peroxidase-like domain lacks heme binding and peroxidase activity established that DUOX1 is an H₂O₂ generator rather than a peroxidase, distinguishing it from invertebrate orthologs.

    Evidence Purified recombinant peroxidase domains from human and C. elegans, heme-binding and enzymatic assays

    PMID:19460756

    Open questions at the time
    • Structural basis for loss of heme binding not resolved
    • Whether the peroxidase-like domain has non-enzymatic regulatory functions unknown
  4. 2009 High

    Linking DUOX1 to EGFR transactivation via ADAM17-mediated ligand shedding and IL-8 production placed DUOX1 upstream of a major epithelial innate defense signaling axis.

    Evidence siRNA knockdown in airway epithelial cells, catalase compartmentalization, EGFR/ERK inhibitors, ADAM17 activation assays upon bacterial stimulation

    PMID:19386603

    Open questions at the time
    • Direct molecular targets of DUOX1-derived H₂O₂ in EGFR transactivation not identified
    • Cysteine residue specificity unknown
  5. 2010 High

    Discovering that DUOX1 binds IP3R1 and that its H₂O₂ inactivates SHP-2 to amplify ZAP-70 phosphorylation revealed DUOX1 as a redox-dependent positive feedback regulator of TCR signaling.

    Evidence Co-immunoprecipitation of DUOX1–IP3R1, siRNA/shRNA knockdown in CD4+ T cells with TCR signaling readouts

    PMID:20682913

    Open questions at the time
    • Whether SHP-2 oxidation is direct or indirect not fully resolved
    • Stoichiometry and dynamics of DUOX1-IP3R1 interaction unknown
  6. 2010 High

    Showing that Duox1 knockout mice have altered bladder pressure responses and that TRPV4-triggered Ca²⁺ activates DUOX1-dependent H₂O₂ in urothelium extended DUOX1 function beyond thyroid and airway to mechanosensory epithelial biology.

    Evidence Duox1 gene-deficient mice, TRPV4 agonists, H₂O₂ measurement in urothelial cells, bladder pressure assays

    PMID:21146788

    Open questions at the time
    • Downstream targets of DUOX1-derived H₂O₂ in urothelium unidentified
    • Whether DUOX1 is required for normal bladder function or only stress responses unclear
  7. 2013 High

    Identifying Src and ADAM17 as direct cysteine-oxidized targets of DUOX1-derived H₂O₂ provided the first molecular mechanism for how DUOX1 activates the EGFR transactivation pathway.

    Evidence Thiol-specific biotin labeling to detect cysteine oxidation in Src and ADAM17, Co-IP of Src–DUOX1, P2Y2R antagonists in airway epithelial cells

    PMID:23349873

    Open questions at the time
    • Specific oxidized cysteine residues in Src and ADAM17 not mapped
    • Whether oxidation is direct (DUOX1-proximal) or relay-mediated unknown
  8. 2014 High

    Global proteomic identification of DUOX1-dependent S-glutathionylated targets (β-actin, Prx1, Src, MKP-1) broadened the scope of DUOX1 redox signaling beyond EGFR to cytoskeletal dynamics and MAPK regulation.

    Evidence Biotin-GSH labeling with avidin purification and proteomics in DUOX1-shRNA H292 cells and DUOX1-deficient mouse tracheal epithelial cells

    PMID:24624333

    Open questions at the time
    • Functional validation of individual S-glutathionylation events incomplete
    • Kinetics and reversibility of these modifications not characterized
  9. 2015 High

    Demonstrating that ionizing radiation sustains DUOX1-dependent H₂O₂ via p38 MAPK/IL-13 upregulation, causing persistent DNA damage, revealed DUOX1 as an amplifier of radiation-induced genotoxicity in thyroid.

    Evidence siRNA knockdown and catalase treatment in thyroid cells, p38 inhibitors, γH2AX foci quantification after irradiation

    PMID:25848056

    Open questions at the time
    • Whether DUOX1-mediated DNA damage contributes to thyroid carcinogenesis in vivo not tested
    • Direct H₂O₂ target causing DSBs not identified
  10. 2016 High

    Pinpointing EGFR Cys-797 as the redox-sensitive activating residue and distinguishing sulfenylation (activating) from S-glutathionylation provided the precise molecular mechanism of DUOX1-mediated EGFR activation.

    Evidence In vitro kinase assays with recombinant Src/EGFR, C797S mutagenesis, dimedone-based sulfenylation trapping, DUOX1 siRNA in airway cells

    PMID:27650496

    Open questions at the time
    • Whether sequential sulfenylation-to-S-glutathionylation serves as a regulatory switch in vivo unknown
    • Structural basis of Cys-797 accessibility not resolved
  11. 2016 High

    In vivo allergen models showed that DUOX1-dependent EGFR cysteine oxidation drives airway remodeling including mucous metaplasia and fibrosis, and that DUOX1 silencing could reverse established disease, establishing DUOX1 as a therapeutic target in allergic airway disease.

    Evidence DUOX1-deficient mice, intratracheal siRNA delivery, HDM allergen model with histological and molecular readouts

    PMID:27812543

    Open questions at the time
    • Specific epithelial vs. immune cell contribution not dissected
    • Long-term safety of DUOX1 inhibition in innate defense not evaluated
  12. 2016 Medium

    Finding that DUOX1 silencing induces EMT, loss of E-cadherin, and resistance to EGFR inhibitors in lung cancer cells suggested DUOX1 maintains epithelial differentiation, with its loss promoting a mesenchymal/stem-like phenotype.

    Evidence Stable RNAi knockdown and overexpression in lung epithelial/cancer cell lines, EMT marker analysis, migration/invasion assays

    PMID:27694834

    Open questions at the time
    • Mechanism linking DUOX1 loss to E-cadherin downregulation not defined
    • In vivo tumor models with DUOX1 genetic manipulation lacking
    • Causal relationship vs. correlation with EGFR inhibitor resistance not fully resolved
  13. 2017 Medium

    Showing that ATG5 controls DUOX1 apical membrane trafficking without affecting total protein levels revealed an autophagy-dependent mechanism for DUOX1 localization and functional activation.

    Evidence siRNA knockdown of ATG5 and DUOX1 in primary human airway epithelial cells, EPR spectroscopy, confocal localization, OVA mouse model

    PMID:28982074

    Open questions at the time
    • Direct interaction between ATG5/autophagy machinery and DUOX1 not demonstrated
    • Whether this is canonical or non-canonical autophagy unclear
  14. 2018 High

    Demonstrating that Duox1⁻/⁻ B cells show enhanced proliferation upon BCR stimulation established DUOX1-derived H₂O₂ as a negative regulator of B cell expansion, revealing a cell-extrinsic antiproliferative role.

    Evidence Duox1 KO mice, CD19+ B cell isolation, BCR+IL-4 stimulation, proliferation and Ig isotype assays, extracellular catalase phenocopy

    PMID:30559322

    Open questions at the time
    • Molecular target of H₂O₂ in B cell proliferation control not identified
    • Whether effect is autocrine or paracrine not fully resolved
  15. 2019 Medium

    Characterizing the DUOX1 R1307Q and DUOXA1 R56W disease-associated mutations as reducing H₂O₂ output confirmed that both subunits are functionally required and that mutations in either can impair DUOX1 activity.

    Evidence Functional H₂O₂ assays with transfected mutant constructs, protein expression analysis

    PMID:31428054

    Open questions at the time
    • Clinical significance of these variants not established with patient phenotyping
    • Structural basis of R1307Q impairment unknown
  16. 2020 High

    Cryo-EM structures of the DUOX1-DUOXA1 complex revealed the lipid-mediated NADPH-binding pocket, electron transfer path, and an inactive dimer-of-dimers state, providing the first atomic-level understanding of DUOX1 catalysis and oligomeric regulation.

    Evidence Cryo-EM of mouse DUOX1-DUOXA1 in apo and NADPH-bound states with biochemical validation

    PMID:32929281

    Open questions at the time
    • Active monomeric complex structure not captured
    • Calcium-bound EF-hand conformation and activation transition not resolved structurally
  17. 2021 High

    Discovering that DUOX1-derived H₂O₂ stabilizes phospho-Smad3 by blocking its NEDD4L-mediated ubiquitination provided a mechanistic link between DUOX1 and profibrotic TGF-β signaling amplification.

    Evidence DUOX1-deficient mice, Smad3 phosphorylation and ubiquitination assays, Co-IP of phospho-Smad3 with NEDD4L in primary lung fibroblasts

    PMID:32764116

    Open questions at the time
    • Whether DUOX1 directly oxidizes NEDD4L or phospho-Smad3 to block interaction not determined
    • Relevance to non-pulmonary fibrosis settings untested
  18. 2021 High

    Identifying DUOX1 as an NAADP synthase that converts NAADPH to NAADP revealed a previously unrecognized enzymatic activity and connected DUOX1 to global Ca²⁺ signaling during T cell activation.

    Evidence In vitro NAADP formation assay, conditional Duoxa1/Duoxa2 and individual Duox KO mouse T cells, Ca²⁺ microdomain and global imaging

    PMID:34784249

    Open questions at the time
    • Whether NAADP synthesis is physiologically significant relative to H₂O₂ production unknown
    • Structural basis of NAADPH recognition not defined
  19. 2022 High

    Conditional myeloid-specific DUOX1 deletion demonstrated a macrophage-intrinsic role in driving type 2 allergic inflammation, separating DUOX1's immune cell function from its epithelial role.

    Evidence LysM-Cre conditional KO mice, HDM allergen model, type 2 cytokine and macrophage recruitment quantification

    PMID:35654836

    Open questions at the time
    • Molecular mechanism of DUOX1 action in macrophage polarization not defined
    • Whether DUOX1 acts through H₂O₂ or NAADP in macrophages not tested
  20. 2024 High

    Demonstrating that DUOXA1 N-glycosylation controls DUOX1 apical vs. basolateral sorting resolved how the maturation factor directs DUOX1 to the correct membrane domain.

    Evidence Co-expression in polarized MDCK cells, N-glycosylation mutants of DUOXA1, domain-swap experiments, immunofluorescence

    PMID:39126279

    Open questions at the time
    • Glycan structures required for apical sorting not characterized
    • Whether glycosylation-dependent sorting operates identically in all epithelial tissues not tested
  21. 2026 High

    Myeloid-specific DUOX1 ablation attenuated pulmonary fibrosis through loss of Src cysteine oxidation in macrophages, establishing a DUOX1→Src oxidation→profibrotic activation axis that drives macrophage-fibroblast cross-talk.

    Evidence LysM-Cre conditional KO, BMDM migration and profibrotic assays, Src cysteine oxidation biotin-labeling, Src inhibitor rescue, collagen quantification

    PMID:40986746

    Open questions at the time
    • Specific Src cysteine residue(s) oxidized by DUOX1 in macrophages not mapped
    • Whether EGFR ligand shedding by macrophages is the dominant paracrine mechanism not confirmed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of calcium-induced DUOX1 activation (transition from inactive dimer-of-dimers to active state), the physiological importance of NAADP synthesis relative to H₂O₂ production, and the identity of specific oxidized cysteine residues in Src and NEDD4L that mediate DUOX1 signaling.
  • Active-state structure of DUOX1-DUOXA1 not resolved
  • Relative contributions of NAADP vs. H₂O₂ enzymatic activities to downstream biology unknown
  • Precise cysteine targets on Src, ADAM17, and NEDD4L mediating DUOX1 signaling not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 4 GO:0140096 catalytic activity, acting on a protein 3
Localization
GO:0005886 plasma membrane 4
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-168256 Immune System 4
Partners
ADAM17ATG5DUOXA1EGFRITPR1NEDD4LSHP2SRC
Complex memberships
DUOX1-DUOXA1

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 DUOX1 activity is calcium-dependent, requiring functional EF-hand motifs, and is specifically stimulated by cAMP/PKA signaling via phosphorylation of Ser955, whereas DUOX2 is regulated by PKC/phorbol esters. Co-expression with maturation factor DUOXA1 is required for membrane expression and enzymatic activity. Functional H2O2 assay with co-expression of DUOX1/DUOXA1, site-directed mutagenesis of EF-hand motifs, forskolin stimulation, phosphorylation mapping, confirmed in human thyroid cells The Journal of biological chemistry High 19144650
2020 Cryo-EM structures of mouse DUOX1-DUOXA1 complex reveal atomic details of DUOX1-DUOXA1 interaction, a lipid-mediated NADPH-binding pocket, and the electron transfer path. A dimer-of-dimers configuration represents an inactive state, indicating an oligomerization-dependent regulatory mechanism. Cryo-EM structure determination in absence and presence of NADPH substrate, biochemical analysis of oligomeric states Nature structural & molecular biology High 32929281
2010 DUOX1 binds to inositol 1,4,5-trisphosphate receptor 1 (IP3R1) in 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 in TCR signaling. Co-immunoprecipitation of DUOX1 with IP3R1, siRNA knockdown, stable shRNA knockdown, measurement of H2O2 production, TCR signaling readouts (ZAP-70 phosphorylation, Ca2+ entry, ERK activation, cytokine production) Science signaling High 20682913
2013 ATP-mediated DUOX1 activation involves P2Y2 receptor stimulation, which recruits Src and DUOX1 into a signaling complex. DUOX1-derived H2O2 oxidizes cysteine residues within Src and ADAM17, activating the sheddase to release EGFR ligands, leading to EGFR transactivation, ERK/NF-κB activation, and IL-8 production. siRNA and shRNA silencing of DUOX1, thiol-specific biotin labeling to detect cysteine oxidation of Src and ADAM17, P2Y2R antagonists, Co-IP of Src and DUOX1, EGFR transactivation assays PloS one High 23349873
2009 The human DUOX1 N-terminal peroxidase-like domain (residues 1–593) does not bind heme and has no intrinsic peroxidase activity when expressed in isolation, unlike its C. elegans ortholog which covalently binds heme and has modest peroxidase activity. Baculovirus expression and purification of isolated peroxidase domains from human and C. elegans DUOX1, heme-binding assays, peroxidase activity assays, superoxide dismutase activity assays The Journal of biological chemistry High 19460756
2016 ATP-dependent EGFR transactivation involves sequential sulfenylation then S-glutathionylation of Cys residues in EGFR and Src via DUOX1-derived H2O2. Sulfenylation (not S-glutathionylation) is the activating modification; the C797S EGFR variant abolishes H2O2-induced kinase activity enhancement, confirming Cys-797 as the redox-sensitive regulatory residue. In vitro kinase assay with recombinant Src and EGFR treated with H2O2 or GSSG, C797S EGFR mutagenesis, dimedone-based sulfenylation trapping, siRNA/shRNA DUOX1 silencing in airway cells The Journal of biological chemistry High 27650496
2014 DUOX1 is critical for ATP-stimulated transient H2O2 production and protein S-glutathionylation in airway epithelial cells. Identified S-glutathionylated targets include β-actin, peroxiredoxin 1, Src, and MAPK phosphatase 1, linking DUOX1 to cytoskeletal dynamics and MAPK signaling in cell migration. Biotin-tagged GSH cell labeling, avidin purification, global proteomics, DUOX1 shRNA in H292 cells and primary tracheal epithelial cells from DUOX1-deficient mice Redox biology High 24624333
2009 ATP-mediated DUOX1 activation in airway epithelial cells leads to intracellular H2O2-dependent EGFR/ERK activation and ADAM17-mediated EGFR ligand shedding, resulting in IL-8 production in response to bacterial stimuli. Catalase (extracellular and intracellular), EGFR/ERK inhibitors, siRNA knockdown of DUOX1, measurement of ATP release, ADAM17 activation, and IL-8 release upon bacterial stimuli The Journal of biological chemistry High 19386603
2016 DUOX1 mediates allergen-induced persistent EGFR activation through cysteine oxidation within EGFR and Src, driving amphiregulin production, mucous metaplasia, subepithelial fibrosis, and airway remodeling. Targeted siRNA or pharmacological inhibition of DUOX1 reversed established allergic inflammation. DUOX1-deficient mice, DUOX1-targeted siRNA intratracheal delivery, pharmacological NADPH oxidase inhibitors, HDM allergen mouse model, measurement of EGFR cysteine oxidation JCI insight High 27812543
2021 DUOX1-derived H2O2 promotes TGF-β1/Smad3 signaling by preventing phospho-Smad3 degradation. Mechanistically, DUOX1 inhibits the interaction between phospho-Smad3 and the ubiquitin ligase NEDD4L, preventing NEDD4L-mediated ubiquitination and proteasomal targeting of phospho-Smad3. Primary human and mouse lung fibroblasts, DUOX1-deficient mice (DUOX1+/-, DUOX1-/-), TGF-β1 stimulation, Smad3 phosphorylation/ubiquitination assays, Co-IP of phospho-Smad3 with NEDD4L The European respiratory journal High 32764116
2021 DUOX1 and DUOX2 synthesize NAADP from NAADPH in vitro, functioning as NAADP-forming enzymes. In T cells, DUOX1 and DUOX2 (but not NOX1 or NOX2) are required for global Ca2+ signaling 4–12 min after TCR activation, while DUOX2 specifically controls early Ca2+ microdomains in the first 15 s. In vitro enzymatic assay of NAADP formation, mouse T cells with conditional knockout of Duoxa1/Duoxa2, Duox1 KO, Duox2 KO, and Nox1/Nox2 KO; Ca2+ imaging (local microdomains and global) Science signaling High 34784249
2010 DUOX1 is the NADPH oxidase responsible for calcium-stimulated H2O2 production in urothelial cells. TRPV4 calcium channel activation triggers calcium signals that stimulate DUOX1-dependent H2O2 production, and Duox1 knockout mice show altered pressure responses in the urinary bladder. DUOX1 gene-deficient mouse model, selective TRPV4 agonists, H2O2 measurement in urothelial cells, bladder pressure response assays Free radical biology & medicine High 21146788
2007 Duox1 is the main source of H2O2 in the rat thyroid cell line PCCl3. siRNA-mediated silencing of Duox1 reduces H2O2 production, and re-expression of rat Duox1 (but only partial rescue with human DUOX1) restores enzymatic activity. siRNA knockdown of Duox1 in PCCl3 cells, H2O2 production assays, lentiviral re-expression rescue experiments, Western blotting for glycosylated protein Experimental cell research High 17643428
2024 DUOX1 apical sorting in polarized epithelial cells depends on its maturation factor DUOXA1. N-glycosylation of DUOXA1 is required for correct apical targeting of DUOX1; glycosylation-defective DUOXA1 causes DUOX1 mistargeting to the basolateral membrane. Co-expression in MDCK polarized epithelial cells, N-glycosylation mutants of DUOXA1, immunofluorescence localization, domain-swap experiments between DUOXA1 and DUOXA2 Genes to cells High 39126279
2015 DUOX1-derived H2O2 promotes Cxcl8 expression and late-phase neutrophil recruitment via a JNK/c-JUN/AP-1 signaling pathway and histone modifications (H3K4me3, H3K9ac, H3K9me3) at the cxcl8 promoter, but not via ERK or NF-κB. Zebrafish in vivo model (ortholog), Duox1 morpholino knockdown, H2O2 exposure, pharmacological inhibitors of JNK/ERK/NF-κB, chromatin immunoprecipitation (ChIP) for histone modifications at cxcl8 promoter Journal of immunology Medium 25582859
2015 Ionizing radiation activates p38 MAPK, which increases IL-13 expression, leading to upregulation of DUOX1 and sustained DUOX1-dependent H2O2 production for days after irradiation. This persistent H2O2 production causes DNA double-strand breaks and growth arrest; catalase pretreatment or DUOX1 siRNA knockdown abrogates IR-induced DNA damage. Human thyroid cell line and primary thyrocytes, siRNA knockdown of DUOX1, catalase treatment, p38 MAPK inhibitors, measurement of H2O2, DNA damage markers (γH2AX), dose-dependent irradiation Proceedings of the National Academy of Sciences of the United States of America High 25848056
2007 DUOX1 expression and its maturation factor DUOXA1 are developmentally regulated in human fetal lung alveolar type II cells, with strong induction by DCI (dexamethasone/cAMP/IBMX) hormone mixture. DUOX1 localizes to the apical cell pole and mediates H2O2 and acid production in differentiated type II cells. siRNA knockdown of DUOX1 in human fetal lung cells, DCI differentiation, apical localization by immunofluorescence, H2O2 production assays, DPI inhibitor, transepithelial electrical measurements American journal of physiology. Lung cellular and molecular physiology Medium 17337509
2014 Testosterone activates DUOX1 in skin keratinocytes via GPRC6A receptor, which couples to Gq protein to generate IP3 and intracellular Ca2+ mobilization, leading to DUOX1-dependent H2O2 production and caspase-3-mediated apoptosis. GPRC6A siRNA silencing, Ca2+ imaging, H2O2 measurement, caspase-3 activation assay, 3D skin equivalent model The Journal of biological chemistry Medium 25164816
2017 Autophagy proteins, specifically ATG5, regulate DUOX1 localization to the apical membrane in airway epithelial cells during chronic IL-13 stimulation. ATG5 depletion reduces DUOX1-dependent intracellular superoxide production without affecting total DUOX1 protein levels, indicating autophagy controls DUOX1 trafficking rather than expression. siRNA knockdown of DUOX1 and ATG5 in primary human tracheobronchial epithelial cells, OVA mouse model, EPR spectroscopy for superoxide, LC3BII autophagosome marker, confocal immunostaining of DUOX1 localization Redox biology Medium 28982074
2016 DUOX1 silencing in lung epithelial cells causes loss of E-cadherin, epithelial-to-mesenchymal transition (EMT) features, increased vimentin/collagen, and resistance to EGFR tyrosine kinase inhibitors. Conversely, DUOX1 overexpression in A549 cells reverses EMT. DUOX1 silencing also increases cancer stem cell markers CD133 and ALDH1. RNAi-mediated stable DUOX1 knockdown and overexpression, morphology assessment, barrier function, E-cadherin/vimentin protein measurement, migration and anchorage-independent growth assays, in vivo invasion model Oncogenesis Medium 27694834
2018 Duox1-derived H2O2 negatively regulates proliferative activity of primary splenic B cells. BCR stimulation with IL-4 upregulates Duox1 expression and H2O2 production; Duox1-/- B cells show enhanced proliferation without change in Ig isotype production. Extracellular catalase mimics the Duox1-/- proliferative phenotype. Duox1-/- mice, CD19+ B cell isolation, BCR stimulation + IL-4, H2O2 measurement, proliferation assay, in vivo immunization with T cell-dependent and -independent antigens, catalase treatment Journal of immunology High 30559322
2016 DUOX1 and Duox1/2 mediate PDGF-induced intracellular H2O2 production and PKB/Akt phosphorylation in fibroblasts and mesenchymal stromal cells, driving cell migration. Silencing Duox1/2 reduces PDGF-stimulated H2O2, Akt phosphorylation, and migration without affecting ERK1/2. Real-time PCR for NOX isoforms, siRNA silencing of Duox1/2 or Nox4, live H2O2 imaging, migration assays, Western blotting for Akt and ERK phosphorylation PloS one Medium 27110716
2022 Macrophage-intrinsic DUOX1 contributes to type 2 inflammation, mucus metaplasia, and macrophage recruitment during chronic allergen-driven inflammation. Conditional DUOX1 deletion in monocyte/macrophage lineage impaired type 2 cytokine production and macrophage activation in chronic HDM-driven allergic airway inflammation. Conditional cell-type-specific DUOX1 knockout (monocyte/macrophage lineage using Cre-lox), HDM allergen mouse model, type 2 cytokine measurement, mucus staining, macrophage recruitment assays Mucosal immunology High 35654836
2026 Macrophage-intrinsic DUOX1 mediates profibrotic macrophage activation through oxidative activation of Src kinase via cysteine oxidation, promoting MoMac recruitment, collagen production, and EGFR ligand production for macrophage-fibroblast cross-talk. Conditional myeloid-specific DUOX1 ablation dramatically attenuated pulmonary fibrosis. LysM-Cre conditional DUOX1 KO, BMDM in vitro migration and profibrotic activation assays, Src cysteine oxidation by biotin-labeling, saracatinib (Src inhibitor) treatment, collagen quantification, oxygen saturation measurement American journal of respiratory cell and molecular biology High 40986746
2018 DUOX1-mediated H2O2 production regulates sodium transport in H441 bronchiolar epithelial cells. Tonic DUOX1-derived H2O2 activates amiloride-sensitive ENaC currents in dome-forming cells, while H2O2 feeds back negatively on ENaC gene expression. siRNA/DUOX1 knockdown, exogenous catalase, H2O2 dose-response, nystatin-perforated whole-cell patch-clamp for ENaC currents, RT-PCR, immunocytochemistry Acta physiologica Medium 30052308
2023 HIF-2α promotes DUOX1 transcription in response to arsenic exposure; DUOX1-derived ROS suppresses GPX4 expression, promoting ferroptosis and kidney injury. Dual luciferase assay confirmed HIF-2α directly drives DUOX1 promoter activity. siRNA knockdown of DUOX1 in HK-2 cells, dual luciferase reporter assay, in vivo mouse model, GPX4 western blotting, ROS/iron quantification The Science of the total environment Medium 37879473
2019 DUOX1 R1307Q missense mutation and DUOXA1 R56W missense mutation each decrease DUOX1 protein expression and H2O2 generation, demonstrating that intact DUOXA1 is required for full DUOX1 H2O2-generating activity. Functional H2O2 generation assays with transfected mutant DUOX1/DUOXA1 constructs, RT-PCR and protein expression analysis Frontiers in endocrinology Medium 31428054

Source papers

Stage 0 corpus · 52 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 194 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 175 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 78 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 61 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 52 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 49 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 49 27650496
2017 Autophagy regulates DUOX1 localization and superoxide production in airway epithelial cells during chronic IL-13 stimulation. Redox biology 44 28982074
2021 Dual NADPH oxidases DUOX1 and DUOX2 synthesize NAADP and are necessary for Ca2+ signaling during T cell activation. Science signaling 43 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
2012 Reactive oxygen species regulate the levels of dual oxidase (Duox1-2) in human neuroblastoma cells. PloS one 33 22523549
2014 Testosterone stimulates Duox1 activity through GPRC6A in skin keratinocytes. The Journal of biological chemistry 32 25164816
2020 Structures of mouse DUOX1-DUOXA1 provide mechanistic insights into enzyme activation and regulation. Nature structural & molecular biology 31 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 25 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
2023 ZC3H13 reduced DUOX1-mediated ferroptosis in laryngeal squamous cell carcinoma cells through m6A-dependent modification. Tissue & cell 16 37536262
2021 DUOX1 in mammalian disease pathophysiology. Journal of molecular medicine (Berlin, Germany) 16 33704512
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 15 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 6 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
2015 Site-specific Effects of DUOX1-Related Peroxidase on Intercellular Apoptosis Signaling. Anticancer research 3 26504019
2025 DUOX1 inhibits the progression of rheumatoid arthritis by regulating the NF-κB pathway in vitro. Allergologia et immunopathologia 2 40088033
2025 Geniposide Suppresses Tumor Progression Through DUOX1-Mediated Ferroptosis in Hepatocellular Carcinoma. The American journal of Chinese medicine 2 40621626
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
2025 Eosinophil-airway epithelial cell crosstalk reveals the eosinophil-mediated DUOX1 upregulation in a murine allergic inflammation setting. Journal of leukocyte biology 1 39447011
2023 DUOX1 Gene Missense Mutation Confers Susceptibility on Type 2 Amiodarone-Induced Thyrotoxicosis. International journal of molecular sciences 1 36835420
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