title: A peroxiredoxin promotes H2O2 signaling and oxidative stress resistance by oxidizing a thioredoxin family protein.
abstract: H2O2 can cause oxidative damage associated with age-related diseases such as diabetes and cancer but is also used to initiate diverse responses, including increased antioxidant gene expression. Despite significant interest, H2O2-signaling mechanisms remain poorly understood. Here, we present a mechanism for the propagation of an H2O2 signal that is vital for the adaptation of the model yeast, Schizosaccharomyces pombe, to oxidative stress. Peroxiredoxins are abundant peroxidases with conserved antiaging and anticancer activities. Remarkably, we find that the only essential function for the thioredoxin peroxidase activity of the Prx Tpx1(hPrx1/2) in resistance to H2O2 is to inhibit a conserved thioredoxin family protein Txl1(hTxnl1/TRP32). Thioredoxins regulate many enzymes and signaling proteins. Thus, our discovery that a Prx amplifies an H2O2 signal by driving the oxidation of a thioredoxin-like protein has important implications, both for Prx function in oxidative stress resistance and for responses to H2O2.
authors.affiliation: Institute for Cell and Molecular Biosciences, Newcastle University, Framlington Place, Newcastle NE2 4HH, Tyne and Wear, UK.
authors.forename: Jonathon D
authors.initials: JD
authors.lastname: Brown
authors.affiliation: Institute for Cell and Molecular Biosciences, Newcastle University, Framlington Place, Newcastle NE2 4HH, Tyne and Wear, UK.
authors.forename: Alison M
authors.initials: AM
authors.lastname: Day
authors.affiliation: Institute for Cell and Molecular Biosciences, Newcastle University, Framlington Place, Newcastle NE2 4HH, Tyne and Wear, UK.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Taylor
authors.affiliation: Institute for Cell and Molecular Biosciences, Newcastle University, Framlington Place, Newcastle NE2 4HH, Tyne and Wear, UK.
authors.forename: Lewis E
authors.initials: LE
authors.lastname: Tomalin
authors.affiliation: Institute for Cell and Molecular Biosciences, Newcastle University, Framlington Place, Newcastle NE2 4HH, Tyne and Wear, UK. Electronic address: b.a.morgan@ncl.ac.uk.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Morgan
authors.affiliation: Institute for Cell and Molecular Biosciences, Newcastle University, Framlington Place, Newcastle NE2 4HH, Tyne and Wear, UK. Electronic address: e.a.veal@ncl.ac.uk.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Veal
mesh_terms: D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D018384:Oxidative Stress; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; C105096:Pap1 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; C515985:Tpx1 protein, S pombe; C000591027:Txl1 protein, S pombe; D013879:Thioredoxins; D006861:Hydrogen Peroxide; D054464:Peroxiredoxins