Based on our work in yeast, we propose that Prdx (Tpx1) can act as a peroxide transducer to increase activation of the P38 MAPK (Sty1) in fission yeast by two independent mechanisms: first, (as depicted on the right-hand side) the reduction of Prdx-Prdx disulfides promotes oxidation of thioredoxin (Trx)20and, accordingly, the oxidation of the MAPK phosphatase (MKP) Pyp1, inhibiting Pyp1’s activity toward Sty1. Thioredoxin reduces disulfide bonds in oxidized proteins, with Trx-MKP disulfide complexes, as illustrated, an expected intermediate in the reduction of MKP. However, our data in trx1mutant cells (Figure 2) are consistent with oxidized Trx1 accepting electrons from reduced Pyp1 (as indicated “?”). Second, (as depicted on the left-hand side) Prdx-P38 MAPK complexes stabilize interactions with the MAPKK (Wis1) to provide a MAPKK-MAPK “signaling island” that allows increased autophosphorylation and canonical autophosphorylation of the MAPKK. In yeast, we show that constitutive Sty1-Tpx1 complex formation drives downstream signaling that accelerated entry into mitosis (Figure 5C). See alsoFigure S7.
