| 2007 |
PKA phosphorylates NoxA1 at Ser172 and Ser461, which enhances NoxA1 binding to 14-3-3 proteins (specifically 14-3-3ζ) and induces dissociation of NoxA1 from the Nox1 complex at the plasma membrane, thereby inhibiting Nox1-dependent ROS production. Elevation of cAMP inhibits, and PKA inhibition enhances, Nox1-dependent ROS production through effects on NoxA1. |
Site-directed mutagenesis, transfected HEK293 cell model, endogenous Nox1 in colon cell lines, co-immunoprecipitation, cAMP manipulation |
The Journal of biological chemistry |
High |
17913709
|
| 2010 |
MAP kinases phosphorylate NoxA1 at Ser282, and PKC and PKA phosphorylate NoxA1 at Ser172. These phosphorylations occur basally and down-regulate constitutive NOX1 activity. Single mutants S172A and S282A up-regulate NOX1-derived ROS, and double mutant S172A/S282A further increases ROS. Phosphorylation at these sites decreases NoxA1 binding to both NOX1 and Rac1. |
In vitro kinase assays, site-directed mutagenesis, phosphopeptide mapping, transfected HEK293 cell model, ROS measurement |
FASEB journal |
High |
20110267
|
| 2010 |
c-Src phosphorylates NoxA1 at Tyr110 and Tks4 at Tyr508; abolishing these phosphorylations blocks the NoxA1–Tks4 interaction and decreases Nox1-dependent ROS generation. Phosphomimetic mutants of both NoxA1 and Tks4 rescue SrcYF-induced invadopodia formation and ECM degradation, while unphosphorylatable mutants block it. NoxA1 interaction with Tks4 and Tks5 scaffold proteins is Src-activity dependent. |
Site-directed mutagenesis (phosphomimetic and unphosphorylatable mutants), co-immunoprecipitation, ROS measurement, invadopodia/ECM degradation assays in human colon cancer cells |
Molecular biology of the cell |
High |
20943948
|
| 2006 |
Noxa1 (the p67phox homologue) is expressed in the cytosolic fraction of mouse vascular smooth muscle cells (VSMC) and co-localizes to the membrane when co-expressed with Noxo1. Antisense knockdown of Noxa1 attenuates basal and agonist (bFGF, EGF)-induced ROS production in mouse VSMC, establishing Noxa1 as the central activator subunit of the smooth muscle NADPH oxidase. |
Western blot, immunohistochemistry, fluorescent fusion protein localization, antisense knockdown, L012 chemiluminescence ROS assay |
Free radical biology & medicine |
Medium |
16814099
|
| 2013 |
A peptide mimicking the putative activation domain of NOXA1 (NoxA1ds) potently and selectively inhibits Nox1-derived superoxide production in a reconstituted cell-free system and in whole cells, with no effect on Nox2, Nox4, Nox5, or xanthine oxidase. FRET experiments show NoxA1ds disrupts the direct binding interaction between Nox1 and NOXA1, identifying the NOXA1 activation domain as the critical interface for NOX1 complex assembly. |
Cell-free reconstituted Nox1 system, cytochrome c reduction, Amplex Red fluorescence, EPR, FRET (Nox1-YFP/NOXA1-CFP), ELISA, FRAP, confocal microscopy with FITC-labeled peptide |
The Journal of biological chemistry |
High |
24187133
|
| 2010 |
The isolated tandem SH3 domains of NOXO1 bind p22phox with high affinity, likely in a superSH3 conformation, and the C-terminal tail of NOXO1 competes for p22phox binding, thereby contributing to NOX1 regulation. The NOXO1–NOXA1 interaction differs molecularly from the p47phox–p67phox interaction of the phagocytic oxidase, suggesting functional differences between the two systems. |
Isothermal titration calorimetry (ITC), quantitative characterization of protein-protein interactions in vitro |
PloS one |
Medium |
20454568
|
| 2007 |
The NOXA1 SH3 domain is not required for NOX1 activation but modulates the kinetics of active complex formation: truncated NOXA1 lacking SH3 activates NOX1 at an accelerated rate compared to wild-type. A heptapeptide insertion into the SH3 domain (from the NOXA1(inhib) splice variant) inhibits NOXA1 activity by ~90%, acts as a transdominant inhibitor, and abrogates SH3 domain binding to NOXO1 and p47phox. |
Transfection into K562 cells stably expressing NOX1/NOXO1, kinetic superoxide generation assays, deletion and insertion mutagenesis, pulldown binding assays |
Free radical biology & medicine |
Medium |
17602954
|
| 2008 |
In airway epithelial cells, Noxa1 associates with plasma membrane-bound Duox (Duox1) and acts as an inhibitory regulator of Duox activity. Calcium flux promotes Duox activation by causing dissociation of Noxa1 from Duox. Knockdown of Noxa1 increases basal H2O2 generation. Mutation of a proline-rich domain in the Duox C-terminus (a potential Noxa1-SH3 interaction motif) up-regulates H2O2 production, and the Noxa1 activation domain is not required for Duox regulation. |
siRNA knockdown, Duox1 reconstitution in model cell lines, mutagenesis of Noxa1 and Duox1, H2O2 measurement, mucociliary airway epithelium model |
The Journal of biological chemistry |
Medium |
18606821
|
| 2013 |
PKC-mediated phosphorylation of Noxo1 at Thr341 (directly phosphorylated by PKC in vitro) facilitates Noxo1 interaction with Noxa1, and this interaction is required for PMA-dependent enhancement of Nox1 superoxide production. Alanine substitution at Thr341 reduces both Noxo1 phosphorylation and Nox1-catalyzed superoxide production. |
In vitro PKC kinase assay, site-directed mutagenesis (T341A), pulldown binding assay between Noxo1 and Noxa1, superoxide production assay |
The FEBS journal |
Medium |
23957209
|
| 2014 |
PKCβ1 phosphorylates Nox1 at Thr429 in response to TNFα, and this phosphorylation facilitates association of Nox1 with the NoxA1 activation domain. This Nox1-NoxA1 interaction is necessary for NADPH oxidase complex assembly, ROS production, and vascular smooth muscle cell migration. |
Mass spectrometry (phosphosite identification), pharmacological PKC inhibition, siRNA silencing of PKCβ1, site-directed mutagenesis (T429), isothermal titration calorimetry (NoxA1ds binding), VSMC migration assay, ROS measurement |
Circulation research |
High |
25228390
|
| 2008 |
siRNA-mediated knockdown of NOXA1 in human vascular endothelial cells potently decreases ROS generation induced by oxidized LDL and angiotensin II, establishing NOXA1 as essential for NAD(P)H oxidase-dependent ROS production in endothelial cells downstream of LOX-1 signaling. |
siRNA knockdown, dihydroethidium ROS assay, RT-PCR |
Endothelium |
Medium |
18568954
|
| 2012 |
In a pure reconstituted cell-free system using purified cytochrome b558 (Nox2+p22phox), Rac(Q61L), and Noxo1, Noxa1 activates Nox2 with lower efficiency than p67phox: higher EC50, one-third Vmax, lower FAD affinity, and reduced stability of the active complex. These kinetic differences distinguish Noxa1 from the canonical Nox2 activator p67phox. |
In vitro reconstituted cell-free NADPH oxidase system with purified proteins, kinetic analysis, FAD affinity measurement |
Archives of biochemistry and biophysics |
High |
22244833
|
| 2018 |
SMC-specific genetic deletion of Noxa1 in Apoe-/- mice reduces vascular ROS, attenuates TNFα-induced VSMC proliferation and migration, and decreases expression of KLF4 transcription factor and its downstream targets VCAM1, CCL2, and MMP2 in atherosclerotic lesions, placing NOXA1-dependent NOX1 activity upstream of KLF4-mediated VSMC phenotypic switching to macrophage-like cells. |
Conditional SMC-specific Noxa1 knockout mouse, endovascular injury model, Western diet atherosclerosis model, immunofluorescence, ROS measurement, VSMC proliferation/migration assays |
Redox biology |
High |
30576919
|
| 2022 |
Principal cell-specific Noxa1 knockout mice fail to increase ENaC activity in response to angiotensin II, and pharmacological NOX1 inhibition (ML171) abolishes ANG II-dependent ENaC stimulation, establishing that NOXA1/NOX1 signaling mediates ANG II-dependent activation of the epithelial sodium channel in renal principal cells of the distal nephron. |
Principal cell-specific Noxa1 conditional knockout mice, patch-clamp electrophysiology on freshly isolated split-open tubules, ML171 pharmacological inhibition, losartan AT1R blockade |
American journal of physiology. Renal physiology |
High |
36201326
|
| 2022 |
NOXA1 is present in Henle's thick ascending limb and distal nephron epithelial cells. Systemic Noxa1 deletion reduces basal systolic blood pressure and attenuates ANG II-induced increases in renal ENaC levels, ENaC activation in collecting duct principal cells, and sodium retention, with sex-specific differences (males more affected than females). |
Noxa1 global knockout mice, telemetry blood pressure measurement, ANG II infusion, immunofluorescence, siRNA knockdown of Noxa1 in renal epithelial cell line, ENaC activity assay |
Antioxidants & redox signaling |
Medium |
34714114
|
| 2025 |
Knockdown of Noxa1 in radiotherapy-resistant colorectal cancer cells decreases expression of SLC7A11 and GPX4, increases cellular ROS levels, induces ferroptosis, and sensitizes cells to radiotherapy, placing NOXA1 upstream of the glutathione metabolic pathway (SLC7A11/GPX4 axis) as a suppressor of ferroptosis. |
siRNA knockdown of Noxa1 in CRC cell lines, Western blot for SLC7A11 and GPX4, ROS measurement, ferroptosis assay, radiotherapy sensitivity assay, GSVA pathway analysis |
International journal of medical sciences |
Low |
40084254
|
| 2025 |
ERVWE1 (human endogenous retrovirus W envelope protein) upregulates USF2 transcription factor, which enhances NOXA1 transcription. NOXA1 in turn promotes macroautophagy (increased LC3B II/I ratio, enhanced autophagosome formation, reduced SQSTM1) and inhibits micromitophagy by suppressing PINK1, Parkin, and PDHA1 expression in the context of schizophrenia-related pathology. |
Cellular and molecular experiments in neuronal context, LC3B assay, autophagosome formation assay, SQSTM1/PINK1/Parkin/PDHA1 expression, bioinformatics (GSE53987), clinical serum measurements |
Virologica Sinica |
Low |
40419114
|