Peroxiredoxin Ahp1 acts as a receptor for alkylhydroperoxides to induce disulfide bond formation in the Cad1 transcription factor.
Reactive oxygen species (ROS) generated during cellular metabolism are toxic to cells. As a result, cells must be able to identify ROS as a stress signal and induce stress response pathways that protect cells from ROS toxicity. Recently, peroxiredoxin (Prx)-induced relays of disulfide bond formation have been identified in budding yeast, namely the disulfide bond formation of Yap1, a crucial transcription factor for oxidative stress response, by a specific Prx Gpx3 and by a major Prx Tsa1. Here, we show that an atypical-type Prx Ahp1 can act as a receptor for alkylhydroperoxides, resulting in activation of the Cad1 transcription factor that is homologous to Yap1. We demonstrate that Ahp1 is required for the formation of intermolecular Cad1 disulfide bond(s) in both an in vitro redox system and in cells treated with alkylhydroperoxide. Furthermore, we found that Cad1-dependent transcriptional activation of the HSP82 gene is dependent on Ahp1. Our results suggest that, although the Gpx3-Yap1 pathway contributes more strongly to resistance than the Ahp1-Cad1 pathway, the Ahp1-induced activation of Cad1 can function as a defense system against stress induced by alkylhydroperoxides, possibly including lipid peroxides. Thus, the Prx family of proteins have an important role in determining peroxide response signals and in transmitting the signals to specific target proteins by inducing disulfide bond formation.
Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi 980-0861, Japan.
Kenta
K
Iwai
Akira
A
Naganuma
Shusuke
S
Kuge
D047369:Chromatin Immunoprecipitation; D004220:Disulfides / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D005979:Glutathione Peroxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015151:Immunoblotting; D047468:Immunoprecipitation; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010544:Peroxidases / Q000378:metabolism; D054464:Peroxiredoxins / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D020122:tert-Butylhydroperoxide / Q000494:pharmacology*
C515936:AHP1 protein, S cerevisiae; C082904:CAD1 protein, S cerevisiae; D004220:Disulfides; D016877:Oxidants; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D020122:tert-Butylhydroperoxide; D006861:Hydrogen Peroxide; D010544:Peroxidases; C496253:Tsa1 protein, S cerevisiae; D054464:Peroxiredoxins; D005979:Glutathione Peroxidase; C494438:HYR1 protein, S cerevisiae