| 1999 |
NOX1 (originally Mox1) encodes a homologue of the catalytic subunit gp91phox of the phagocyte NADPH oxidase and generates superoxide in non-phagocytic cells; overexpression in NIH3T3 cells increases superoxide production, cell growth rate, anchorage-independent growth, and tumor formation in athymic mice, while antisense NOX1 decreases superoxide generation and serum-stimulated growth in smooth muscle cells. |
Overexpression and antisense inhibition in NIH3T3 and vascular smooth muscle cells; superoxide measurements; tumor formation assay in athymic mice |
Nature |
High |
10485709
|
| 2001 |
H2O2 (derived from NOX1-generated superoxide via dismutation) acts as the key intracellular signal mediating NOX1-driven cell growth and transformation; co-expression of catalase with NOX1 reverses the transformed appearance, normalizes growth rate, prevents tumor formation, and restores >60% of NOX1-regulated genes to normal levels. |
Co-expression of human catalase with NOX1 in NIH3T3 cells; H2O2 and O2- measurements; gene expression profiling; tumor assays in athymic mice |
Proceedings of the National Academy of Sciences of the United States of America |
High |
11331784
|
| 2001 |
NOX1 mediates the early phase of angiotensin II- and PDGF-induced superoxide production in vascular smooth muscle cells and is required for activation of the redox-sensitive signaling molecules p38 MAPK and Akt by Ang II; antisense NOX1 adenovirus completely inhibited this early superoxide phase and downstream redox signaling without affecting redox-independent pathways. |
Antisense adenoviral knockdown of NOX1 in VSMCs; superoxide measurement; Western blot for p38 MAPK and Akt phosphorylation |
Circulation research |
High |
11348997
|
| 2002 |
NOX1 requires cytosolic activator proteins to generate superoxide; two novel colon-enriched proteins NOXO1 (p47phox homologue, lacks autoinhibitory domain and PKC phosphorylation sites) and NOXA1 (p67phox homologue, lacks first SH3 domain, has hydrophobic stretch) were identified; co-expression of NOX1 with NOXO1 and NOXA1 leads to constitutive high-level superoxide generation, whereas replacing NOXO1 with p47phox restores stimulus-dependence. |
Co-expression of NOX1 with p47phox/p67phox or novel NOXO1/NOXA1 in heterologous cells; superoxide measurements; cDNA cloning |
The Journal of biological chemistry |
High |
12473664
|
| 2002 |
NOX1-derived ROS trigger the angiogenic switch by markedly upregulating VEGF mRNA (in cultured cells and tumors) and inducing VEGFR1/VEGFR2 in vascular cells; matrix metalloproteinase activity is also induced; VEGF induction is abolished by catalase co-expression, implicating H2O2 as the signaling intermediate. |
NOX1 overexpression in DU-145 prostate cells; VEGF mRNA measurement; immunostaining of VEGF receptors in tumors; catalase co-expression; MMP activity assay |
Proceedings of the National Academy of Sciences of the United States of America |
High |
11805326
|
| 2004 |
Oncogenic Ras upregulates NOX1 expression via the MEK-MAPK pathway, and NOX1-generated ROS are required for Ras-induced transformation; siRNA knockdown of NOX1 blocks anchorage-independent growth, morphological transformation, and tumor formation in athymic mice caused by activated Ras. |
siRNA knockdown of NOX1 in Ras-transformed cells; MEK inhibitor; anchorage-independent growth assay; tumor formation in athymic mice |
Cancer research |
High |
15150115
|
| 2004 |
NOX1 activity in growth factor-stimulated cells is mediated by sequential activation of PI3K → βPix (a Rac GEF that constitutively associates with the C-terminal region of NOX1) → Rac1 (which binds to the C-terminal region of NOX1 in a growth factor-dependent manner); siRNA depletion of βPix blocks both Rac1 activation and ROS production. |
Co-immunoprecipitation of NOX1 C-terminal region with βPix and Rac1; siRNA knockdown of βPix and Nox1; ROS measurement; PI3K and other pathway inhibitors |
Molecular and cellular biology |
High |
15121857
|
| 2004 |
NOX1 physically associates with p22phox in vascular smooth muscle cells; co-immunoprecipitation and confocal colocalization demonstrate the two proteins are preassembled at the plasma membrane and submembrane areas in unstimulated cells, and NADPH-driven superoxide production depends on coexpression of both subunits. |
Co-immunoprecipitation of HA-tagged NOX1 with p22phox; confocal colocalization; ESR spin-probe measurement of NADPH-driven superoxide in cells expressing both subunits |
Free radical biology & medicine |
High |
15477006
|
| 2005 |
NOX1 is required for angiotensin II-induced superoxide production and the resultant pressor response in vivo; Nox1-knockout mice show significantly blunted blood pressure elevation and aortic superoxide production in response to Ang II, with preserved endothelium-dependent relaxation and cGMP levels, indicating NOX1-derived ROS reduce NO bioavailability to mediate hypertension. |
Nox1 knockout mice; Ang II infusion; telemetric blood pressure measurement; superoxide production in aorta; endothelium-dependent relaxation; cGMP measurement; L-NAME experiments |
Circulation |
High |
16246966
|
| 2007 |
TNF treatment induces formation of a signaling complex containing TRADD, RIP1, NOX1, and the small GTPase Rac1 in mouse fibroblasts undergoing necrosis; RIP1 is essential for NOX1 recruitment to this complex; dominant-negative TRADD or Rac1 and NOX1 siRNA each prevent TNF-induced superoxide generation and necrotic cell death. |
Co-immunoprecipitation demonstrating TRADD/RIP1/NOX1/Rac1 complex; RIP1-deficient fibroblasts; dominant-negative mutants; NOX1 siRNA; superoxide measurement; cell death assay |
Molecular cell |
High |
17560373
|
| 2009 |
The C-terminal cytosolic tail of NOX1 confers cytosolic subunit-dependent activation, while the N-terminal transmembrane portion determines plasma membrane localization and superoxide (vs. H2O2) release; Nox1 N-terminus is proteolytically cleaved; chimeric NOX1/NOX4 proteins reveal that a Nox4 cytosolic tail fused to Nox1 transmembrane domain renders NOX1 constitutively active. |
Chimeric NOX1/NOX4 constructs expressed in HEK293 cells; TIRF microscopy for subcellular localization; Myc-tag processing analysis; ROS measurements |
Antioxidants & redox signaling |
High |
19061439
|
| 2009 |
Tks4 and Tks5 (c-Src substrate proteins) are functional p47phox-related organizers that selectively support NOX1 (and NOX3) activity; Tks proteins interact with the NOXA1 activator through an SH3 domain-mediated interaction; endogenous Tks4 is required for Rac GTPase- and NOX1-dependent ROS production and for NOX1 recruitment to invadopodia in DLD1 colon cancer cells. |
Reconstituted cellular systems; co-immunoprecipitation (Tks-NoxA1 SH3 interaction); siRNA knockdown of Tks4; ROS measurement; invadopodia formation assay |
Science signaling |
High |
19755710
|
| 2010 |
LRRC8A (a component of volume-regulated anion channels) co-localizes with and co-immunoprecipitates with NOX1 and its p22phox subunit in vascular smooth muscle cells; LRRC8A siRNA suppresses TNFα-induced extracellular superoxide production by NOX1, TNFR1 endocytosis, and JNK phosphorylation; extracellular superoxide (not H2O2) is the critical oxidant enabling TNFR1 endocytosis. |
Co-immunoprecipitation; siRNA knockdown; VRAC inhibitor; extracellular SOD/catalase discrimination; TNFR1 endocytosis assay; JNK phosphorylation |
Free radical biology & medicine |
High |
27838438
|
| 2010 |
TNFα-induced NOX1 activation in smooth muscle cells requires dynamin-dependent receptor endocytosis, whereas thrombin-mediated NOX1 activation occurs outside endosomes and requires EGFR transactivation; both pathways converge on PI3K-Akt-ATF-1 signaling in a NOX1- and dynamin-dependent manner. |
NOX1 shRNA; dominant-negative dynamin; endosomal ROS measurement; EGFR transactivation assay; PI3K-Akt-ATF-1 pathway analysis |
Antioxidants & redox signaling |
High |
19737091
|
| 2010 |
NOX1 upregulates EGFR and TGF-α expression through an Src-ERK positive feedback loop and a parallel p38 MAPK-AKT pathway, driving autocrine growth of liver tumor cells; NOX1 knockdown reduces EGFR/TGF-α mRNA and EGFR phosphorylation, and antioxidants or NADPH oxidase inhibition attenuates autocrine growth. |
NOX1 siRNA; antioxidants; pharmacological NADPH oxidase inhibition; EGFR/TGF-α mRNA and protein measurement; EGFR phosphorylation; pathway inhibitors |
The Journal of biological chemistry |
High |
20525691
|
| 2010 |
NOX1-derived ROS promote invadopodia formation (extracellular matrix-degrading actin-rich structures) in human colon cancer cells; the selective NOX1 small-molecule inhibitor ML171 (2-acetylphenothiazine) blocks NOX1-dependent ROS generation and invadopodia formation at nanomolar concentrations with selectivity over other NOX isoforms; NOX1 overexpression rescues ML171 inhibition, confirming selectivity. |
High-throughput screening; ML171 pharmacological inhibition; NOX1 overexpression rescue; invadopodia assay; isoform selectivity panel |
ACS chemical biology |
High |
20715845
|
| 2011 |
Annexin A1 (ANXA1) activates epithelial NOX1 through formyl peptide receptor 1 (FPR1) signaling; NOX1-derived ROS oxidatively inactivate phosphatases PTEN and PTP-PEST, leading to activation of FAK and paxillin, thereby promoting epithelial cell migration and mucosal wound repair; intestinal epithelial-specific Nox1 knockout mice show defects in mucosal wound repair. |
Intestinal epithelial-specific Nox1 knockout mice; ANXA1 administration; phosphatase activity (PTEN, PTP-PEST); FAK and paxillin activation; cell migration assay; in vivo wound repair |
The Journal of clinical investigation |
High |
23241962
|
| 2012 |
DNA damage-induced ROS generation is mediated through the H2AX-NOX1/Rac1 pathway; H2AX overexpression or NCS-induced DNA damage increases NOX1 activity partly by reducing the interaction between the NOX1 activator NOXA1 and its inhibitor 14-3-3ζ; NOX1 knockdown (but not NOX4) reduces ROS and cell death induced by H2AX accumulation. |
siRNA knockdown of NOX1 and NOX4; dominant-negative Rac1; NADPH oxidase inhibitor DPI; ROS measurement; co-immunoprecipitation (NOXA1/14-3-3ζ interaction); cell death assay |
Cell death & disease |
High |
22237206
|
| 2012 |
In rat REF52 cells, oncogenic Ras upregulates NOX1 through the Ras/MEK pathway to increase intracellular ROS, which transduce senescence signals activating the p53 and p16Ink4a pathways; NOX1 siRNA blocks Ras-induced senescence (β-galactosidase activity, growth arrest), DNA damage response, and p38MAPK activation; this is confirmed in Nox1 knockout mouse embryo fibroblasts. |
siRNA knockdown of NOX1; Nox1 knockout MEFs; senescence markers (β-gal, p53, p16); DNA damage assay; p38 MAPK phosphorylation; MEK inhibitor |
Genes to cells : devoted to molecular & cellular mechanisms |
High |
23216904
|
| 2014 |
Protein kinase C-β1 phosphorylates NOX1 at threonine 429 in response to TNFα; this phosphorylation facilitates association of NOX1 with the NoxA1 activation domain, is necessary for NADPH oxidase complex assembly, ROS production, and vascular smooth muscle cell migration; PKCβ1 siRNA abolishes TNFα-mediated ROS production and VSMC migration. |
Mass spectrometry identifying phosphorylation site; PKCβ1 inhibitor and siRNA; site-directed mutagenesis (T429A); isothermal titration calorimetry (NOX1/NoxA1 interaction); ROS measurement; VSMC migration assay |
Circulation research |
High |
25228390
|
| 2016 |
Peroxiredoxin 6 (Prdx6) is a novel binding partner of NOXA1, identified by yeast two-hybrid using the NOXA1 SH3 domain as bait; Prdx6 binds to and stabilizes NOXA1 via SH3 domain interaction; both the peroxidase (C47S) and phospholipase A2 (S32A) activities of Prdx6 are required for NOX1 activation and NOX1-mediated cell migration; the PLA2 transition-state inhibitor MJ-33 suppresses NOX1 activity. |
Yeast two-hybrid; co-immunoprecipitation; Prdx6 knockdown and overexpression; enzymatic mutants (C47S, S32A); MJ-33 inhibitor; superoxide measurement; cell migration assay |
Free radical biology & medicine |
High |
27094494
|
| 2016 |
CRISPR/Cas9-mediated knockout of p22phox (CYBA) abolishes NOX1 (and NOX4) activity but not NOX5 activity; p22phox is required for maturation and activity of NOX1; rescue with human or rat p22phox, but not DUOXA1/A2, restores NOX1-dependent superoxide production. |
CRISPR/Cas9 knockout; reconstitution with human/rat p22phox and DUOXA1/A2; ROS measurements (H2O2 and superoxide); multiple p22phox mutation analysis |
Redox biology |
High |
27614387
|
| 2017 |
NOX1-derived ROS in the ventral tegmental area (VTA) mediate depressive-like behaviors by oxidizing NMDA receptor subunit NR1 (at C744); NOX1-derived ROS suppress NMDA-induced BDNF upregulation in cortical neurons via NR1 oxidation; NR1 C744A mutant is resistant to H2O2-mediated suppression of BDNF; redox proteomics identified NR1 as the NOX1 target. |
Nox1 knockout mice; miRNA delivery to VTA; chronic social defeat stress and corticosterone models; redox proteome analysis; cortical neuron culture with H2O2 and NR1 C744A mutant; BDNF mRNA and DNA methylation measurements |
The Journal of neuroscience |
High |
28314819
|
| 2013 |
NOX1 is required for normal apoptosis of pulmonary arterial smooth muscle cells (PASMCs) through regulation of the voltage-gated K+ channel Kv1.5 and intracellular potassium levels; Nox1-deficient mice develop spontaneous pulmonary vascular remodeling with reduced PASMC apoptosis and decreased Kv1.5 protein; re-expression of rat NOX1 transgene in knockout mice rescues impaired apoptosis and Kv1.5 levels. |
Nox1 knockout mice; Nox1 transgene rescue; flow cytometry and TUNEL for apoptosis; Kv1.5 protein measurement; intracellular potassium measurement |
Arteriosclerosis, thrombosis, and vascular biology |
High |
24233492
|
| 2011 |
NOX1 mediates morphine-induced analgesic tolerance by attenuating opioid pharmacology; Nox1-deficient mice show augmented morphine analgesia and suppressed tolerance; NOX1-derived ROS regulate GTPase activity in the dorsal spinal cord, impair G-protein coupling, promote PKC isoform membrane translocation, enhance RGS9-2 phosphorylation, and facilitate Gαi2/RGS9-2/14-3-3 complex formation. |
Nox1 knockout mice; [35S]GTPγS binding; morphine-stimulated GTPase activity; PKC membrane translocation assay; RGS9-2 phosphorylation; co-immunoprecipitation (Gαi2/RGS9-2/14-3-3) |
The Journal of neuroscience |
High |
22159121
|
| 2007 |
STAT1 and STAT3 directly bind to GAS elements in the NOX1 promoter (demonstrated by chromatin immunoprecipitation) and transactivate NOX1 expression in human vascular smooth muscle cells; JAK/STAT pathway regulates IFNγ-induced NOX1 activity; JAK/STAT blockade reduces NOX1 subunit transcription. |
Chromatin immunoprecipitation; promoter-luciferase assays; STAT1/STAT3 overexpression; JAK/STAT inhibitors; NOX activity measurement |
Arteriosclerosis, thrombosis, and vascular biology |
High |
19834108
|
| 2007 |
MEF2B transcription factor binds to a consensus MEF2 site in the NOX1 promoter (-146 to -125) in response to prostaglandin F2α; MEF2B is downstream of ATF-1 in a PGF2α/PDGF-induced cascade (ATF-1→MEF2B→NOX1); MEF2B siRNA suppresses NOX1 expression and reduces VSMC superoxide production. |
Promoter deletion analysis; MEF2 site binding; MEF2B siRNA; ATF-1 siRNA; RT-PCR of NOX1; superoxide assay in VSMCs |
The FEBS journal |
High |
17822438
|
| 2007 |
Nox1, together with its partner proteins NOXO1 and NOXA1, is localized predominantly to the Golgi apparatus in human gastric adenocarcinoma cells (intestinal-type, diffuse-type, and signet-ring cell carcinoma), with nuclear localization also observed in diffuse-type; co-expression of Nox1, NOXO1, NOXA1, and p22phox is specific to gastric cancer cells and absent from normal gastric mucosa. |
Immunohistochemistry; confocal microscopy showing subcellular localization; immunofluorescence |
Free radical biology & medicine |
Medium |
18037128
|
| 2007 |
NOX1 overexpression induces genome instability; co-expression of NOX1 with NOXO1 and NOXA1 in HeLa cells increases 8-oxoguanine levels and causes a 3-fold increase in HPRT mutation rate, without upregulating DNA repair enzymes, suggesting ROS-mediated saturation of repair capacity. |
Co-expression of hNOX1/NOXO1/NOXA1 in HeLa cells; ROS measurement; 8-oxoguanine quantification; HPRT mutation rate; repair enzyme expression analysis |
Free radical biology & medicine |
Medium |
17963706
|
| 2010 |
NOX1 inhibits p53 proapoptotic transcriptional activity and p53 Lys382 acetylation through a SIRT1-dependent mechanism; NOX1 activates SIRT1 deacetylase activity, and SIRT1 deacetylase-defective mutant (SIRT1HY) renders cells unresponsive to NOX1-dependent inhibition of p53; recovery of HIPK2 function downregulates NOX1 and rescues p53 Lys382 acetylation. |
siRNA knockdown of NOX1 and SIRT1; SIRT1 inhibitor nicotinamide; SIRT1HY deacetylase-dead mutant; p53 Lys382 acetylation and transcriptional activity assays; HIPK2 rescue experiment |
Free radical biology & medicine |
Medium |
20171273
|
| 2014 |
NOX1 is the key NADPH oxidase regulating GPVI-dependent ROS production in platelets; pharmacological inhibition of NOX1 with ML171 blocks GPVI (collagen-related peptide)-induced ROS, thromboxane A2 production (via p38 MAPK signaling), and reduces collagen-mediated thrombus formation at arterial shear in ex vivo perfusion; Nox2-deficient mice confirm NOX1 specificity for this pathway. |
ML171 pharmacological inhibition; Nox2-deficient mice; p38 MAPK inhibition; TxA2 measurement; platelet aggregation assay; ex vivo perfusion thrombus model |
Redox biology |
Medium |
24494191
|
| 2016 |
NOX1 directly interacts with and stabilizes ADAM17 (TACE) from ubiquitin-mediated degradation; NOX1 overexpression activates the ADAM17-EGFR-PI3K-AKT signaling pathway to promote colon cancer cell migration and invasion; co-immunoprecipitation demonstrates the NOX1-ADAM17 physical interaction. |
Co-immunoprecipitation; NOX1 overexpression; ADAM17 ubiquitination assay; EGFR-PI3K-AKT pathway Western blot; migration/invasion assay |
European review for medical and pharmacological sciences |
Medium |
27874952
|
| 2021 |
NOX1-derived ROS mediate colonic stem cell (CSC) proliferation through redox-dependent activation of EGFR signaling; NOX1 expression is CSC-specific and restricted to proliferating CSCs; in the absence of NOX1, CSCs fail to generate ROS and have reduced proliferation; NOX1 expression is regulated by Toll-like receptor activation in response to the microbiota, establishing a TLR-NOX1-EGFR axis. |
NOX1 knockout colonoids and mice; single-cell ROS measurement; EGFR signaling readout; TLR stimulation; CSC-specific NOX1 expression analysis |
Cell reports |
High |
33826887
|
| 2022 |
Renal NOXA1-dependent NOX1 activity is required for Ang II-induced upregulation of epithelial sodium channel (ENaC) in collecting duct principal cells and sodium retention; Noxa1 knockout mice show attenuated Ang II-induced hypertension and impaired ENaC activation; aldosterone induces ROS and Noxa1/Scnn1a expression and ENaC activity through NOXA1-NOX1, abolished by Noxa1 siRNA. |
Noxa1 knockout mice; telemetric blood pressure; ENaC activity measurement; Na+ excretion assay; Noxa1 siRNA in renal epithelial cells; ROS measurement |
Antioxidants & redox signaling |
High |
34714114
|
| 2021 |
NOX1-derived ROS drive spermatogonial stem cell (SSC) self-renewal under normoxia through a ROS-BCL6B-NOX1 feed-forward pathway; under hypoxia, NOX1-derived (not mitochondrial) ROS influence HIF1A expression in undifferentiated spermatogonia; Nox1-deficient SSCs proliferate poorly under hypoxia but normally under normoxia; CDKN1A depletion rescues impaired Nox1-deficient SSC proliferation under hypoxia. |
Nox1 knockout mice and SSC cultures; normoxia/hypoxia conditions; BCL6B expression; HIF1A measurement; CDKN1A siRNA rescue; mitochondrial ROS suppression |
Genes & development |
High |
33446567
|
| 2019 |
NF-κB directly regulates NOXO1 expression in TNF-α-stimulated gastric cancer cells, activating the NOX1 complex; NOX1/ROS signaling increases proliferation of gastric epithelial cells and expands SOX2-positive undifferentiated epithelial stem cells; disruption of Noxo1 in gastritis mouse model suppresses metaplastic hyperplasia and reduces SOX2-positive cells. |
NF-κB inhibition and overexpression; NOXO1 promoter analysis; Noxo1 knockout in K19-C2mE mice; in situ hybridization; SOX2 immunostaining; gastric hyperplasia histology |
Oncogene |
High |
30700829
|
| 2004 |
Helicobacter pylori LPS activates NOX1 in gastric mucosal cells through two distinct events: transcriptional upregulation of Nox1 and NOXO1 mRNAs, and activation of Rac1 (GTP-bound state) via PI3K; a constitutively active Rac1 adenovirus (but not Cdc42) restores PI3K inhibitor-blocked superoxide generation, establishing Rac1 as an essential NOX1 activator. |
Primary guinea pig gastric mucosal cells; Rac1 GTP-loading assay; adenoviral constitutively active Rac1/Cdc42; PI3K inhibitor LY294002; actinomycin D and cycloheximide blocking; superoxide measurement |
American journal of physiology. Cell physiology |
High |
15469954
|
| 2015 |
NOX1 missense variants p.Pro330Ser and p.Asp360Asn found in VEOIBD patients show reduced ROS production compared to wild-type NOX1 despite appropriate cellular localization; cells harboring these variants have defective host resistance to Campylobacter jejuni infection, establishing that NOX1 ROS generation is required for epithelial innate defense. |
Sanger sequencing; ROS generation assay in model cell lines and murine crypts; cellular localization assessment; pathogen infection assay (C. jejuni, EPEC); structural homology modeling |
Cellular and molecular gastroenterology and hepatology |
High |
26301257
|
| 2007 |
The NOX1 promoter region contains a GATA-4/5/6 binding element and overlapping sites for Cdx1/Cdx2 and HNF-1α; these factors show cooperativity in transactivating the NOX1 promoter; GATA-6, HNF-1α, and Cdx2 bind to this chromatin region in CaCo2 cells; their expression gradients in mouse colon parallel the distal-to-proximal NOX1 gradient. |
Promoter-luciferase deletion analysis; in vitro DNA binding; chromatin immunoprecipitation in CaCo2 cells; transcription factor co-transfection cooperativity assay; NOX1 expression gradient analysis in normal and germ-free mice |
Free radical biology & medicine |
High |
18005670
|
| 2011 |
NOX1 is expressed in hepatic stellate cells (HSCs) but not Kupffer cells; NOX1 mediates profibrogenic effects in endogenous liver cells; NOX1-deficient HSCs show decreased ROS generation and fail to upregulate collagen α1(I) and TGF-β in response to angiotensin II; bone marrow chimera experiments confirm that NOX1 acts in endogenous liver cells rather than bone marrow-derived cells. |
Nox1 knockout mice; CCl4 and bile duct ligation hepatic fibrosis models; bone marrow chimeras; HSC and Kupffer cell isolation; ROS generation; collagen/TGF-β measurement |
Hepatology (Baltimore, Md.) |
High |
21384410
|