ArticleMolecular and cellular biology2006
Involvement of Rac1 in activation of multicomponent Nox1- and Nox3-based NADPH oxidases.
Article in Molecular and cellular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.
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Who cites it
104 citing papers in PubMed, 224 citations in OpenAlex.
- Role of NADPH Oxidases as Novel Therapeutic Targets for the Impaired Neurovascular Unit in the Early Stage of Diabetic Retinopathy.International journal of molecular sciences · 2026Review
- Peroxiredoxin 6 Alone or in Combination with Fingolimod Ameliorates EAE.Current neuropharmacology · 2026Article
- Nox3 expression and function in retinal ganglion cells and Amacrine cells.Cellular and molecular life sciences : CMLS · 2025Article
- NOX-NOS crosstalk in the liver-brain axis: Novel insights for redox regulation and neurodegenerative diseases.Redox biology · 2025Review
- Molecular Roles of NADPH Oxidase-Mediated Oxidative Stress in Alzheimer's Disease: Isoform-Specific Contributions.International journal of molecular sciences · 2024Review
- MicroRNA-124-3p Modulates Alpha-Synuclein Expression Levels in a Paraquat-Induced in vivo Model for Parkinson's Disease.Neurochemical research · 2024Article
- NADPH Oxidase 3: Beyond the Inner Ear.Antioxidants (Basel, Switzerland) · 2024Review
- NOX1 and PRDX6 synergistically support migration and invasiveness of hepatocellular carcinoma cells through enhanced NADPH oxidase activity.Advances in redox research · 2023Article
- Exogenous 8-Hydroxydeoxyguanosine Attenuates PMAntioxidants (Basel, Switzerland) · 2023Article
- NOX4-derived ROS are neuroprotective by balancing intracellular calcium stores.Cellular and molecular life sciences : CMLS · 2023Article
- Natural Bioactive Compounds Targeting NADPH Oxidase Pathway in Cardiovascular Diseases.Molecules (Basel, Switzerland) · 2023Review
- The Intestinal Redox System and Its Significance in Chemotherapy-Induced Intestinal Mucositis.Oxidative medicine and cellular longevity · 2022Review
- HACE1-mediated NRF2 activation causes enhanced malignant phenotypes and decreased radiosensitivity of glioma cells.Signal transduction and targeted therapy · 2021Article
- Reactive Oxygen Species in Acute Lymphoblastic Leukaemia: Reducing Radicals to Refine Responses.Antioxidants (Basel, Switzerland) · 2021Review
- Mechanisms underlying unidirectional laminar shear stress-mediated Nrf2 activation in endothelial cells: Amplification of low shear stress signaling by primary cilia.Redox biology · 2021Review
- A small molecule inhibitor of Nox2 and Nox4 improves contractile function after ischemia-reperfusion in the mouse heart.Scientific reports · 2021Article
- Nox3-Derived Superoxide in Cochleae Induces Sensorineural Hearing Loss.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Cross-Talk between Oxidative Stress and mOxidative medicine and cellular longevity · 2021Review
- NOX Inhibitors: From Bench to Naxibs to Bedside.Handbook of experimental pharmacology · 2021Article
- NADPH oxidases: Pathophysiology and therapeutic potential in age-associated pulmonary fibrosis.Redox biology · 2020Review
44 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
Abstract
Several Nox family NADPH oxidases function as multicomponent enzyme systems. We explored determinants of assembly of the multicomponent oxidases Nox1 and Nox3 and examined the involvement of Rac1 in their regulation. Both enzymes are supported by p47phox and p67phox or homologous regulators called Noxo1 and Noxa1, although Nox3 is less dependent on these cofactors for activity. Plasma membrane targeting of Noxa1 depends on Noxo1, through tail-to-tail interactions between these proteins. Noxa1 can support Nox1 without Noxo1, when targeted to the plasma membrane by fusing membrane-binding sequences from Rac1 (amino acids 183 to 192) to the C terminus of Noxa1. However, membrane targeting of Noxa1 is not sufficient for activation of Nox1. Both the Noxo1-independent and -dependent Nox1 systems involve Rac1, since they are affected by Rac1 mutants or Noxa1 mutants defective in Rac binding or short interfering RNA-mediated Rac1 silencing. Nox1 or Nox3 expression promotes p22phox transport to the plasma membrane, and both oxidases are inhibited by mutations in the p22phox binding sites (SH3 domains) of the Nox organizers (p47phox or Noxo1). Regulation of Nox3 by Rac1 was also evident from the effects of mutant Rac1 or mutant Nox3 activators (p67phox or Noxa1) or Rac1 silencing. In the absence of Nox organizers, the Nox activators (p67phox or Noxa1) colocalize with Rac1 within ruffling membranes, independently of their ability to bind Rac1. Thus, Rac1 regulates both oxidases through the Nox activators, although it does not appear to direct the subcellular localization of these activators.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.