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Reference: Ouyang X, et al. (2011) Yap1 activation by H(2)O(2) or thiol-reactive chemicals elicits distinct adaptive gene responses. Free Radic Biol Med 50(1):1-13

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Abstract


The yeast Saccharomyces cerevisiae transcription factor Yap1 mediates an adaptive response to oxidative stress by regulating protective genes. H(2)O(2) activates Yap1 through the Gpx3-mediated formation of a Yap1 Cys303-Cys598 intra-molecular disulfide bond. Thiol-reactive electrophiles can activate Yap1 directly by adduction to cysteine residues in the C-terminal domain containing Cys598, Cys620, and Cys629. H(2)O(2) and N-ethylmaleimide (NEM) showed no cross-protection against each other, while another thiol-reactive chemical, acrolein, elicited Yap1-dependent cross-protection against NEM, but not H(2)O(2). Either Cys620 or Cys629 was sufficient for activation of Yap1 by NEM or acrolein; Cys598 was dispensable for this activation mechanism. To determine whether Yap1 activated by H(2)O(2) or thiol-reactive chemicals elicits distinct adaptive gene responses, microarray analysis was performed on the wildtype strain or its isogenic single deletion strain Deltayap1 treated with either control buffer, H(2)O(2), NEM or acrolein. Sixty-five unique H(2)O(2) and 327 NEM and acrolein Yap1-dependent responsive genes were identified. Functional analysis using single gene deletion yeast strains demonstrated that protection was conferred by CTA1 and CTT1 in the H(2)O(2)-responsive subset, and YDR042C in the NEM and acrolein-responsive subset. These findings demonstrate that the distinct mechanisms of Yap1 activation by H(2)O(2) or thiol-reactive chemicals result in selective expression of protective genes.CI - Copyright (c) 2010. Published by Elsevier Inc.

Reference Type
Journal Article
Authors
Ouyang X, Tran QT, Goodwin S, Wible RS, Sutter CH, Sutter TR
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