Redox regulation of cell signaling by selenocysteine in mammalian thioredoxin reductases

J Biol Chem. 1999 Aug 27;274(35):24522-30. doi: 10.1074/jbc.274.35.24522.


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.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Dinitrochlorobenzene / chemistry
  • Epidermal Growth Factor / pharmacology
  • Fluoresceins / chemistry
  • Gene Expression Regulation, Enzymologic / genetics
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Isoenzymes / chemistry
  • Isoenzymes / genetics
  • Liver / enzymology
  • Male
  • Mass Spectrometry
  • Mice
  • Molecular Sequence Data
  • Oxidation-Reduction
  • Peptide Fragments / analysis
  • Peroxidases
  • RNA, Messenger / metabolism
  • Reactive Oxygen Species / metabolism
  • Recombinant Proteins / genetics
  • Selenocysteine / metabolism*
  • Signal Transduction*
  • Testis / enzymology
  • Thioredoxin-Disulfide Reductase / chemistry
  • Thioredoxin-Disulfide Reductase / genetics*
  • Tumor Cells, Cultured


  • Dinitrochlorobenzene
  • Fluoresceins
  • Isoenzymes
  • Peptide Fragments
  • RNA, Messenger
  • Reactive Oxygen Species
  • Recombinant Proteins
  • Selenocysteine
  • Epidermal Growth Factor
  • 5-iodoacetamidofluorescein
  • Hydrogen Peroxide
  • Peroxidases
  • TXNRD3 protein, human
  • Thioredoxin-Disulfide Reductase

Associated data

  • GENBANK/AF171053
  • GENBANK/AF171054
  • GENBANK/AF171055