ArticleThe Journal of biological chemistry2012
Constitutive NADPH oxidase 4 activity resides in the composition of the B-loop and the penultimate C terminus.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 49 citations in OpenAlex.
- NADPH oxidases: redox regulation of cell homeostasis and disease.Physiological reviews · 2025Review
- Blockade of Activin Receptor IIB Protects Arthritis Pathogenesis by Non-Amplification of Activin A-ACVR2B-NOX4 Axis Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Targeting NOX4 disrupts the resistance of papillary thyroid carcinoma to chemotherapeutic drugs and lenvatinib.Cell death discovery · 2022Article
- NADPH debt drives redox bankruptcy: SLC7A11/xCT-mediated cystine uptake as a double-edged sword in cellular redox regulation.Genes & diseases · 2021Review
- Nox4 Knockout Does Not Prevent Diaphragm Atrophy, Contractile Dysfunction, or Mitochondrial Maladaptation in the Early Phase Post-Myocardial Infarction in Mice.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2021Article
- Inhibiting the Activity of NADPH Oxidase in Cancer.Antioxidants & redox signaling · 2020Article
- NADPH oxidases: Pathophysiology and therapeutic potential in age-associated pulmonary fibrosis.Redox biology · 2020Review
- Reactive Oxygen Species Signaling Promotes Hypoxia-Inducible Factor 1α Stabilization in Sonic Hedgehog-Driven Cerebellar Progenitor Cell Proliferation.Molecular and cellular biology · 2019Article
- Quantitative interaction analysis permits molecular insights into functional NOX4 NADPH oxidase heterodimer assembly.The Journal of biological chemistry · 2018Article
- NADPH Oxidases and Mitochondria in Vascular Senescence.International journal of molecular sciences · 2018Review
- Decoding NADPH oxidase 4 expression in human tumors.Redox biology · 2017Article
- Evolutionary origin and function of NOX4-art, an arthropod specific NADPH oxidase.BMC evolutionary biology · 2017Article
- Genetic disorders coupled to ROS deficiency.Redox biology · 2015Review
- Evolution of NADPH Oxidase Inhibitors: Selectivity and Mechanisms for Target Engagement.Antioxidants & redox signaling · 2015Review
- Ubiquitin C-terminal hydrolase-L1 increases cancer cell invasion by modulating hydrogen peroxide generated via NADPH oxidase 4.Oncotarget · 2015Article
- Oxidative stress and hepatic Nox proteins in chronic hepatitis C and hepatocellular carcinoma.Free radical biology & medicine · 2014Review
- NADPH oxidases in lung health and disease.Antioxidants & redox signaling · 2014Review
- Article
- Detection of superoxide anion and hydrogen peroxide production by cellular NADPH oxidases.Biochimica et biophysica acta · 2014Review
- Angiotensin receptor-mediated oxidative stress is associated with impaired cardiac redox signaling and mitochondrial function in insulin-resistant rats.American journal of physiology. Heart and circulatory physiology · 2013Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Redox regulation of signaling molecules contributes critically to propagation of intracellular signals. The main source providing reactive oxygen species (ROS) for these physiological processes are activated NADPH oxidases (Nox/Duox family). In a pathophysiological context, some NADPH oxidase complexes produce large amounts of ROS either as part of the antimicrobial immune defense or as pathologic oxidative stress in many chronic diseases. Thus, understanding the switch from a dormant, inactive conformation to the active state of these enzymes will aid the development of inhibitors. As exogenously expressed Nox4 represents the only constitutively active enzyme in this family, analysis of structural determinants that permit this active conformation was undertaken. Our focus was directed toward a cell-based analysis of the first intracellular loop, the B-loop, and the C-terminus, two regions of Nox family enzymes that are essential for electron transfer. Mutagenesis of the B-loop identified several unique residues and a polybasic motif that contribute to the catalytic activity of Nox4. By using a multifaceted approach, including Nox4-Nox2 chimeras, mutagenesis, and insertion of Nox2 domains, we show here that the penultimate 22 amino acids of Nox4 are involved in constitutive ROS generation. The appropriate spacing of the C-terminal Nox4 sequence may cooperate with a discrete arginine-based interaction site in the B-loop, providing an intrinsically active interface that could not be disrupted by peptides derived from the Nox4 C-terminus. These results indicate that accessibility for a Nox4-specific peptide inhibitor might be difficult to achieve in vivo.
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