title: A possible biochemical link between NADPH oxidase (Nox) 1 redox-signalling and ERp72.
abstract: Emerging evidence indicates that Nox (NADPH oxidase) 1-generated ROS (reactive oxygen species) play critical regulatory roles in various cellular processes, yet little is known of direct targets for the oxidase. In the present study we show that one of the proteins selectively oxidized in response to Nox1-generated ROS was ERp72 (endoplasmic reticulum protein 72 kDa) with TRX (thioredoxin) homology domains. Oxidation of ERp72 by Nox1 resulted in an inhibition of its reductase activity. EGF treatment of cells stimulated the Nox1 activity and the activated Nox1 subsequently mediated EGF-induced suppression of the ERp72 reductase activity. Co-immunoprecipitation, GST (glutathione transferase) pulldown assays and mutational analysis, indicated that Nox1 associates with ERp72, which involves its N-terminus encompassing a Ca(2+)-binding site and the first TRX-like motif. Furthermore, confocal microscopy showed co-localization between Nox1 and ERp72 at the plasma membrane. These results suggest that Nox1 functionally associates with ERp72, regulating redox-sensitive signalling pathways in a cellular context.
authors.affiliation: Department of Molecular Biology and Biochemistry, Shinshu University Graduate School of Medicine, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Wei Hao
authors.initials: WH
authors.lastname: Shang
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Adachi
authors.forename: Kunitaka
authors.initials: K
authors.lastname: Hirose
authors.forename: David M
authors.initials: DM
authors.lastname: Ferrari
authors.forename: Tohru
authors.initials: T
authors.lastname: Kamata
mesh_terms: D000818:Animals; D019556:COS Cells; D018938:Caco-2 Cells; D002522:Chlorocebus aethiops; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D000074624:NADPH Oxidase 1; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; C062477:endoplasmic reticulum glycoprotein p72; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1