Regulation of the yeast phospholipid hydroperoxide glutathione peroxidase GPX2 by oxidative stress is mediated by Yap1 and Skn7

FEBS Lett. 2004 May 7;565(1-3):148-54. doi: 10.1016/j.febslet.2004.03.091.

Abstract

The GPX2 gene encodes a homologue of phospholipid hydroperoxide glutathione peroxidase in Saccharomyces cerevisiae. The GPX2 promoter contains three elements the sequence of which is completely consistent with the optimal sequence for the Yap1 response element (YRE). Here, we identify the intrinsic YRE that functions in the oxidative stress response of GPX2. In addition, we discovered a cis-acting element (5'-GGCCGGC-3') within the GPX2 promoter proximal to the functional YRE that is necessary for H(2)O(2)-induced expression of GPX2. We present evidence showing that Skn7 is necessary for the oxidative stress response of GPX2 and is able to bind to this sequence. We determine the optimal sequence for Skn7 to regulate GPX2 under conditions of oxidative stress to be 5'-GGC(C/T)GGC-3', and we designate this sequence the oxidative stress-responsive Skn7 response element.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Blotting, Western
  • Carrier Proteins / biosynthesis*
  • DNA Primers / chemistry
  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation, Enzymologic*
  • Genes, Reporter
  • Glutathione Peroxidase / biosynthesis*
  • Glutathione Peroxidase / genetics*
  • Hydrogen Peroxide / pharmacology
  • Lac Operon
  • Models, Genetic
  • Mutagenesis
  • Oxidative Stress*
  • Phosphoproteins / biosynthesis*
  • Point Mutation
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic
  • Protein Binding
  • Response Elements
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae Proteins*
  • Time Factors
  • Transcription Factors / biosynthesis*
  • Transcription Factors / metabolism
  • YAP-Signaling Proteins
  • beta-Galactosidase / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • DNA Primers
  • DNA-Binding Proteins
  • MSN2 protein, S cerevisiae
  • MSN4 protein, S cerevisiae
  • Phosphoproteins
  • SKN7 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • Hydrogen Peroxide
  • GPX2 protein, S cerevisiae
  • Glutathione Peroxidase
  • beta-Galactosidase