title: A major peroxiredoxin-induced activation of Yap1 transcription factor is mediated by reduction-sensitive disulfide bonds and reveals a low level of transcriptional activation.
abstract: Redox reactions involving cysteine thiol-disulfide exchange are crucial for the intracellular monitoring of hydrogen peroxide (H(2)O(2)). Yap1, the master transcription factor for the oxidative stress response in budding yeast, is activated by the formation of disulfide bonds in response to H(2)O(2). Gpx3 (glutathione peroxidase-like protein 3) acts as a receptor for H(2)O(2), and Ybp1 (Yap1-binding protein 1) is crucial for Gpx3-dependent disulfide bond formation in Yap1. We previously reported that Tsa1, a major peroxiredoxin in yeast cells, is required for activation of Yap1 in a widely used yeast strain, W303-1b, carrying the ybp1-1 mutant allele encoding a truncated Ybp1 protein. In the present study, we show that Tsa1 can interact with Yap1 via disulfide linkages and induce the formation of intramolecular disulfide bonds in Yap1 in ybp1-1 cells. The results provide evidence that Prx can have intrinsic activity as an H(2)O(2) receptor and can relay H(2)O(2) as a signal to the Prx target proteins in terms of formation of disulfide linkage. Furthermore, our data reveal that there is more of the reduction-resistant active form of Yap1 (i.e. Yap1 (oxII)) when it is partnered with Gpx3 than with Tsa1. These data support our hypothesis that changes in the redox status of Yap1 to reduction-resistant forms by multiple disulfide bond formation are important for determining the level and duration of Yap1 activity in the dynamic equilibrium of redox reactions in cells exposed to H(2)O(2).
authors.affiliation: Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi 980-0861, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Tachibana
authors.forename: Shoko
authors.initials: S
authors.lastname: Okazaki
authors.forename: Asako
authors.initials: A
authors.lastname: Murayama
authors.forename: Akira
authors.initials: A
authors.lastname: Naganuma
authors.forename: Akio
authors.initials: A
authors.lastname: Nomoto
authors.forename: Shusuke
authors.initials: S
authors.lastname: Kuge
mesh_terms: D004220:Disulfides / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010544:Peroxidases / Q000235:genetics / Q000378:metabolism*; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*
chemical_list: D004220:Disulfides; D016877:Oxidants; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C086677:YAP1 protein, S cerevisiae; D006861:Hydrogen Peroxide; D010544:Peroxidases; C496253:Tsa1 protein, S cerevisiae; D054464:Peroxiredoxins; D005979:Glutathione Peroxidase; C494438:HYR1 protein, S cerevisiae