title: Dissection of a redox relay: H2O2-dependent activation of the transcription factor Pap1 through the peroxidatic Tpx1-thioredoxin cycle.
abstract: In fission yeast, the transcription factor Pap1 undergoes H2O2-dependent oxidation that promotes its nuclear accumulation and the activation of an antioxidant gene program. However, the mechanisms that regulate the sensitivity and selectivity of Pap1 activation by peroxides are not fully understood. Here, we demonstrate that the peroxiredoxin Tpx1, the sensor of this signaling cascade, activates the otherwise unresponsive Pap1 protein once the main cytosolic reduced thioredoxin, Trx1, becomes transiently depleted. In other words, Pap1 works as an alternative electron donor for oxidized Tpx1. We have trapped the very transient Tpx1-Pap1 intermediate in cells depleted in Trx1, as we show here using mass spectrometry. Recycling of Tpx1 by Trx1 is required for the efficient signaling to Pap1, suggesting that the complete cycle of H2O2 scavenging by Tpx1 and further recycling of oxidized Tpx1 by Trx1 is required for full downstream activation of the redox cascade.
authors: Oxidative Stress and Cell Cycle Group, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, C/Dr. Aiguader 88, 08003 Barcelona, Spain.
authors: Isabel A
authors: IA
authors: Calvo
authors: Oxidative Stress and Cell Cycle Group, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, C/Dr. Aiguader 88, 08003 Barcelona, Spain.
authors: Susanna
authors: S
authors: Boronat
authors: Oxidative Stress and Cell Cycle Group, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, C/Dr. Aiguader 88, 08003 Barcelona, Spain.
authors: Alba
authors: A
authors: Domènech
authors: Oxidative Stress and Cell Cycle Group, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, C/Dr. Aiguader 88, 08003 Barcelona, Spain.
authors: Sarela
authors: S
authors: García-Santamarina
authors: Oxidative Stress and Cell Cycle Group, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, C/Dr. Aiguader 88, 08003 Barcelona, Spain.
authors: José
authors: J
authors: Ayté
authors: Oxidative Stress and Cell Cycle Group, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, C/Dr. Aiguader 88, 08003 Barcelona, Spain. Electronic address: elena.hidalgo@upf.edu.
authors: Elena
authors: E
authors: Hidalgo
mesh_terms: D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D010084:Oxidation-Reduction; D000073718:Pancreatitis-Associated Proteins; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; 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; D000073718:Pancreatitis-Associated Proteins; C105096:Pap1 protein, S pombe; C000612141:REG3A protein, human; D029702:Schizosaccharomyces pombe Proteins; C515985:Tpx1 protein, S pombe; C532961:Trx1 protein, S pombe; D013879:Thioredoxins; D006861:Hydrogen Peroxide; D054464:Peroxiredoxins