title: Cellular reactive oxygen species inhibit MPYS induction of IFNβ.
abstract: Many inflammatory diseases, as well as infections, are accompanied by elevation in cellular levels of Reactive Oxygen Species (ROS). Here we report that MPYS, a.k.a. STING, which was recently shown to mediate activation of IFNβ expression during infection, is a ROS sensor. ROS induce intermolecular disulfide bonds formation in MPYS homodimer and inhibit MPYS IFNβ stimulatory activity. Cys-64, -148, -292, -309 and the potential C₈₈xxC₉₁ redox motif in MPYS are indispensable for IFNβ stimulation and IRF3 activation. Thus, our results identify a novel mechanism for ROS regulation of IFNβ stimulation.
authors.affiliation: Integrated Department of Immunology, University of Colorado Denver School of Medicine and National Jewish Health, Denver, Colorado, United States of America.
authors.forename: Lei
authors.initials: L
authors.lastname: Jin
authors.forename: Laurel L
authors.initials: LL
authors.lastname: Lenz
authors.forename: John C
authors.initials: JC
authors.lastname: Cambier
mesh_terms: D000818:Animals; D002460:Cell Line; D003545:Cysteine / Q000737:chemistry; D019281:Dimerization; D004220:Disulfides / Q000737:chemistry; D017930:Genes, Reporter; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D016899:Interferon-beta / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D017382:Reactive Oxygen Species; D000099197:STING Protein
chemical_list: D003545:Cysteine; D004220:Disulfides; D050838:Interferon Regulatory Factor-3; D016899:Interferon-beta; D008565:Membrane Proteins; D017382:Reactive Oxygen Species; C494232:IRF3 protein, human; C494233:Irf3 protein, mouse; C532857:STING1 protein, human; D000099197:STING Protein