title: The emerging role of ROS-generating NADPH oxidase NOX4 in DNA-damage responses.
abstract: The human genome is continuously exposed to such potentially deleterious agents as the highly reactive molecules known as reactive oxygen species (ROS). ROS include superoxide anions (O(2)(-)) and hydrogen peroxide (H(2)O(2)). Over the last decade, the ROS-generating NADPH oxidases (NOXs) have been recognized as one of the main sources of ROS production in numerous human cell types. In addition to regulating normal physiological redox-dependent processes, the NOXs are involved in cellular oxidative stress. In contrast to the other NOXs, the NADPH oxidase NOX4 exists in the immediate environment of the nucleus. There is accumulating evidence for the involvement of NOX4-derived ROS in genomic instability as well as in cancer and other inflammation-related diseases. We recently showed that NOX4 plays a critical role in oncogenic Ras-induced DNA damage. Here we reflect upon the growing awareness of NOX4, review its role in inducing genomic instability, and call attention to its possible role in nuclear redox-sensitive mechanisms underlying DNA-damage signaling and repair.
authors.affiliation: Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, MD 20892, USA.
authors.forename: Urbain
authors.initials: U
authors.lastname: Weyemi
authors.affiliation: UMR 8200 CNRS, University Paris-Sud, Institut Gustave Roussy, 114 rue Edouard Vaillant, Villejuif F-94805, France. Electronic address: dupuy@igr.fr.
authors.forename: Corinne
authors.initials: C
authors.lastname: Dupuy
mesh_terms: D002478:Cells, Cultured; D004249:DNA Damage; D042822:Genomic Instability; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000502:physiology*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human