Back to article: Snf1 cooperates with the CWI MAPK pathway to mediate the degradation of Med13 following oxidative stress


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 1st step towards its release from the nucleus. The second step requires Slt2 to directly phosphorylate Med13-degron742-844, which targets it for ubiquitin mediated degradation by SCFGrr1. Cyclin C-Cdk8 activity is needed to prime the degron before it is recognized by SCFGrr1 [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

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