title: Redox regulation of cell signaling by selenocysteine in mammalian thioredoxin reductases.
abstract: The intracellular generation of reactive oxygen species, together with the thioredoxin and glutathione systems, is thought to participate in redox signaling in mammalian cells. The activity of thioredoxin is dependent on the redox status of thioredoxin reductase (TR), the activity of which in turn is dependent on a selenocysteine residue. Two mammalian TR isozymes (TR2 and TR3), in addition to that previously characterized (TR1), have now been identified in humans and mice. All three TR isozymes contain a selenocysteine residue that is located in the penultimate position at the carboxyl terminus and which is encoded by a UGA codon. The generation of reactive oxygen species in a human carcinoma cell line was shown to result in both the oxidation of the selenocysteine in TR1 and a subsequent increase in the expression of this enzyme. These observations identify the carboxyl-terminal selenocysteine of TR1 as a cellular redox sensor and support an essential role for mammalian TR isozymes in redox-regulated cell signaling.
authors.affiliation: Department of Biochemistry, University of Nebraska, Lincoln, Nebraska 68588, USA.
authors.forename: Q A
authors.initials: QA
authors.lastname: Sun
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.forename: F
authors.initials: F
authors.lastname: Zappacosta
authors.forename: K T
authors.initials: KT
authors.lastname: Jeang
authors.forename: B J
authors.initials: BJ
authors.lastname: Lee
authors.forename: D L
authors.initials: DL
authors.lastname: Hatfield
authors.forename: V N
authors.initials: VN
authors.lastname: Gladyshev
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004137:Dinitrochlorobenzene / Q000737:chemistry; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005452:Fluoresceins / Q000737:chemistry; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics; D008099:Liver / Q000201:enzymology; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000032:analysis; D010544:Peroxidases; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics; D017279:Selenocysteine / Q000378:metabolism*; D015398:Signal Transduction; D013737:Testis / Q000201:enzymology; D013880:Thioredoxin-Disulfide Reductase / Q000737:chemistry / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D004137:Dinitrochlorobenzene; D005452:Fluoresceins; D007527:Isoenzymes; D010446:Peptide Fragments; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D017279:Selenocysteine; D004815:Epidermal Growth Factor; C015296:5-iodoacetamidofluorescein; D006861:Hydrogen Peroxide; D010544:Peroxidases; C500519:TXNRD3 protein, human; D013880:Thioredoxin-Disulfide Reductase