title: Redox sensitivity of the MyD88 immune signaling adapter.
abstract: The transcription factor nuclear factor-κB (NF-κB) mediates expression of key genes involved in innate immunity and inflammation. NF-κB activation has been repeatedly reported to be modulated by hydrogen peroxide (H2O2). Here, we show that the NF-κB-activating signaling adapter myeloid differentiation primary response gene 88 (MyD88) is highly sensitive to oxidation by H2O2and may be redox-regulated in its function, thus facilitating an influence of H2O2on the NF-κB signaling pathway. Upon oxidation, MyD88 forms distinct disulfide-linked conjugates which are reduced by the MyD88-interacting oxidoreductase nucleoredoxin (Nrx). MyD88 cysteine residues functionally modulate MyD88-dependent NF-κB activation, suggesting a link between MyD88 thiol oxidation state and immune signaling.
authors.affiliation: Division of Redox Regulation, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Stottmeier
authors.affiliation: Division of Redox Regulation, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. Electronic address: t.dick@dkfz.de.
authors.forename: Tobias P
authors.initials: TP
authors.lastname: Dick
mesh_terms: D045744:Cell Line, Tumor; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D057809:HEK293 Cells; D006238:Haploidy; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007113:Immunity, Innate; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology*; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology*; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology; D010084:Oxidation-Reduction / Q000187:drug effects; D010088:Oxidoreductases / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction
chemical_list: D004220:Disulfides; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D009687:Nuclear Proteins; D006861:Hydrogen Peroxide; D010088:Oxidoreductases; C105231:nucleoredoxin; D008156:Luciferases; D003545:Cysteine
keywords: Hydrogen peroxide; MyD88; NF-κB; Redox signaling; Thiol oxidation