FIGURE 1: (A) Cdk8 module regulation by the CWI MAPK pathway. H₂O₂ stimulates cell wall sensors Wsc1, Mtl1 and Mid2, leading to activation of Rho1 that in turn triggers the cell wall integrity (CWI) MAPK pathway by activating Protein Kinase C (Pkc1). Activation of this cascade triggers the MAPK, Slt2, to directly phosphorylate cyclin C, an event required for the 1^st step towards its release from the nucleus. The second step requires Slt2 to directly phosphorylate Med13-degron^742-844, which targets it for ubiquitin mediated degradation by SCF^Grr1. Cyclin C-Cdk8 activity is needed to prime the degron before it is recognized by SCF^Grr1 [9]. (B) Outline of the AMPK pathway in yeast. It remains unknown how this pathway is activated in response to H₂O₂ stress. The gray box represents the Snf1 kinase complex (see text for details).

9. Stieg DC, Willis SD, Ganesan V, Ong KL, Scuorzo J, Song M, Grose J, Strich R, Cooper KF (2018). A complex molecular switch directs stress-induced cyclin C nuclear release through SCF(Grr1)-mediated degradation of Med13. Mol Biol Cell 29(3): 363-375. http://dx.doi.org/10.1091/mbc.E17-08-0493