Multistep Disulfide Bond Formation in Yap1 Is Required for Sensing and Transduction of H2O2 Stress Signal

Shoko Okazaki, Tsuyoshi Tachibana, Akira Naganuma, Nariyasu Mano, Shusuke Kuge

Research output: Contribution to journalArticlepeer-review

71 Citations (Scopus)


Redox reactions involving cysteine thiol-disulfide exchange are crucial for sensing intracellular levels of H2O2. However, oxidation-sensitive dithiols are also sensitive to intracellular reducing agents, and disulfide bonds are thus transient. The yeast transcription factor Yap1 is activated by disulfide-induced structural changes in the nuclear export signal in a carboxy-terminal domain. We show herein that the activation of Yap1 by H2O2 requires multistep formation of disulfide bonds. One disulfide bond forms within 15 s in an amino-terminal domain, and then disulfide bonds linking the two domains accumulate. The multiple interdomain disulfide bonds, which result in reduction-resistant Yap1, are required for transduction of the H2O2 stress signal to induce the appropriate level and duration of specific transcription. Our results suggest both a mechanism wherein the H2O2 levels might be sensed by Yap1 and the way in which the NADPH levels might be maintained by altering the redox status of Yap1.

Original languageEnglish
Pages (from-to)675-688
Number of pages14
JournalMolecular Cell
Issue number4
Publication statusPublished - 2007 Aug 17



ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Multistep Disulfide Bond Formation in Yap1 Is Required for Sensing and Transduction of H<sub>2</sub>O<sub>2</sub> Stress Signal'. Together they form a unique fingerprint.

Cite this