Multistep disulfide bond formation in Yap1 is required for sensing and transduction of H2O2 stress signal.
Redox reactions involving cysteine thiol-disulfide exchange are crucial for sensing intracellular levels of H(2)O(2). 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 H(2)O(2) 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 H(2)O(2) stress signal to induce the appropriate level and duration of specific transcription. Our results suggest both a mechanism wherein the H(2)O(2) levels might be sensed by Yap1 and the way in which the NADPH levels might be maintained by altering the redox status of Yap1.
Okazaki
Shoko
S
Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi 980-8578, Japan.
Tachibana
Tsuyoshi
T
Naganuma
Akira
A
Mano
Nariyasu
N
Kuge
Shusuke
S
D004220:Disulfides / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007700:Kinetics; D050505:Mutant Proteins / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D020033:Protein Isoforms / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013816:Thermodynamics; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
D004220:Disulfides; D050505:Mutant Proteins; D020033:Protein Isoforms; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C086677:YAP1 protein, S cerevisiae; D006861:Hydrogen Peroxide