A cysteine-sulfinic acid in peroxiredoxin regulates H2O2-sensing by the antioxidant Pap1 pathway.
The Schizosaccharomyces pombe transcription factor Pap1 regulates antioxidant-gene transcription in response to H2O2. Pap1 activation occurs only at low, but not elevated, H2O2 concentrations that instead strongly trigger the mitogen-activated protein kinase Sty1 pathway. Here, we identify the peroxiredoxin Tpx1 as the upstream activator of Pap1. We show that, at low H2O2 concentrations, this oxidant scavenger can transfer a redox signal to Pap1, whereas higher concentrations of the oxidant inhibit the Tpx1-Pap1 redox relay through the temporal inactivation of Tpx1 by oxidation of its catalytic cysteine to a sulfinic acid. This cysteine modification can be reversed by the sulfiredoxin Srx1, its expression in response to high doses of H2O2 strictly depending on active Sty1. Thus, Tpx1 oxidation to the cysteine-sulfinic acid and its reversion by Srx1 constitutes a previously uncharacterized redox switch in H2O2 signaling, restricting Pap1 activation within a narrow range of H2O2 concentrations.
Vivancos
Ana P
AP
Cell Signaling Unit, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, C/Dr. Aiguader 80, E-08003 Barcelona, Spain.
Castillo
Esther A
EA
Biteau
Benoît
B
Nicot
Carine
C
Ayté
José
J
Toledano
Michel B
MB
Hidalgo
Elena
E
D000975:Antioxidants; D050976:Basic-Leucine Zipper Transcription Factors; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D000073718:Pancreatitis-Associated Proteins; D010544:Peroxidases / Q000737:chemistry / Q000378:metabolism*; D054464:Peroxiredoxins; D010957:Plasmids; D016133:Polymerase Chain Reaction; D012331:RNA, Fungal / Q000235:genetics; D011994:Recombinant Proteins / Q000378:metabolism; D012568:Schizosaccharomyces / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins; D013434:Sulfenic Acids / Q000378:metabolism*
D000975:Antioxidants; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D000073718:Pancreatitis-Associated Proteins; C105096:Pap1 protein, S pombe; C000612141:REG3A protein, human; D012331:RNA, Fungal; D011994:Recombinant Proteins; D029702:Schizosaccharomyces pombe Proteins; D013434:Sulfenic Acids; C515985:Tpx1 protein, S pombe; D006861:Hydrogen Peroxide; D010544:Peroxidases; D054464:Peroxiredoxins; C100870:cysteinesulfenic acid; D003545:Cysteine