Snf1 cooperates with the CWI MAPK pathway to mediate the degradation of Med13 following oxidative stress
Authors:Stephen D. Willis1, David C. Stieg1, Kai Li Ong2, Ravina Shah1,3, Alexandra K. Strich1,4, Julianne H. Grose2 and Katrina F. Cooper1
doi: 10.15698/mic2018.08.641
Volume 5, pp. 357 to 370, published 25/06/2018.
1 Department of Molecular Biology, Graduate School of Biomedical Sciences, Rowan University, Stratford, NJ, 08084, USA.
2 Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602, USA.
3 Current address: Department of Biological Sciences, Rowan University, 201 Mullica Hill Rd, Glassboro, NJ 08028. USA.
4 Current address: Shawnee High School, Medford, New Jersey 08055, USA.
Keywords:
cyclin C, Cdk8, Med13, SCFGrr1, AMPK, Snf1, ubiquitin mediated destruction, signal transduction, H2O2 stress, MAPK
Corresponding Author(s):
Conflict of interest statement:
The authors declare no conflict of interest.
Please cite this article as:
Stephen D. Willis, David C. Stieg, Kai Li Ong, Ravina Shah, Alexandra K. Strich, Julianne H. Grose and Katrina F. Cooper (2018). Snf1 cooperates with the CWI MAPK pathway to mediate the degradation of Med13 following oxidative stress. Microbial Cell: 5(8): 357-370. doi: 10.15698/mic2018.08.641
© 2018 Willis et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
Eukaryotic cells, when faced with unfavorable environmental conditions, mount either pro-survival or pro-death programs. The conserved cyclin C-Cdk8 kinase plays a key role in this decision. Both are members of the Cdk8 kinase module that, along with Med12 and Med13, associate with the core Mediator complex of RNA polymerase II. In Saccharomyces cerevisiae, oxidative stress triggers Med13 destruction, which releases cyclin C into the cytoplasm to promote mitochondrial fission and programmed cell death. The SCFGrr1 ubiquitin ligase mediates Med13 degradation dependent on the cell wall integrity pathway, MAPK Slt2. Here we show that the AMP kinase Snf1 activates a second SCFGrr1 responsive degron in Med13. Deletion of Snf1 resulted in nuclear retention of cyclin C and failure to induce mitochondrial fragmentation. This degron was able to confer oxidative-stress-induced destruction when fused to a heterologous protein in a Snf1 dependent manner. Although snf1∆ mutants failed to destroy Med13, deleting the degron did not prevent destruction. These results indicate that the control of Med13 degradation following H2O2 stress is complex, being controlled simultaneously by CWI and MAPK pathways.