A major peroxiredoxin-induced activation of yap 1 transcription factor is mediated by reduction-sensitive disulfide bonds and reveals a low level of transcriptional activation

Tsuyoshi Tachibana, Shoko Okazaki, Asako Murayama, Akira Naganuma, Akio Nomoto, Shusuke Kuge

Research output: Contribution to journalArticlepeer-review

54 Citations (Scopus)

Abstract

Redox reactions involving cysteine thiol-disulfide exchange are crucial for the intracellular monitoring of hydrogen peroxide (H2O2). Yap1, the master transcription factor for the oxidative stress response in budding yeast, is activated by the formation of disulfide bonds in response to H2O2. Gpx3 (glutathione peroxidase-like protein 3) acts as a receptor for H2O2, 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 H2O2 receptor and can relay H2O2 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 H2O2.

Original languageEnglish
Pages (from-to)4464-4472
Number of pages9
JournalJournal of Biological Chemistry
Volume284
Issue number7
DOIs
Publication statusPublished - 2009 Feb 13

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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