FIG. 2.

Sensing and transducing the H₂O₂ signal by the Orp/AP1-like transcription factor from yeast (Yap) system in yeast. In this system the glutathione peroxidase (GPx)-type peroxidase Orp1 act as sensor for H₂O₂ and becomes oxidized at Cys³⁶ to a sulfenic acid. The sulfenic acid then forms a heterodimeric disulfide bridge with Cys⁵⁹⁸ in Yap1, which in turn is resolved by two more thiol/disulfide exchange reactions (not shown), ultimately resulting in oxidized Yap1 (Yap1S₂) and reduced Orp1. Oxidized Yap1 can bind to the respective enhancer elements in the promoter of target genes, which protect against oxidative challenge. This way Yap1 acts as the transducer of the H₂O₂ signal. An alternative reaction of Orp1 sulfenic acid leads to an intramolecular disulfide bridge (Orp1S₂) that is reduced by thioredoxin (Trx). In this role of a Trx peroxidase Orp1 acts as a modulator of this system. Trx also terminates signaling by reducing Yap1S₂.