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

Microbial Cell
Stephen D WillisKatrina F Cooper

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.

Citations

Mar 12, 2020·Molecular Biology of the Cell·Stephen D WillisKatrina F Cooper
Jul 26, 2019·International Microbiology : the Official Journal of the Spanish Society for Microbiology·Elena Jiménez-GutiérrezHumberto Martín
Jan 10, 2019·Biology·Jan JežekRandy Strich
Sep 17, 2020·The Journal of Biological Chemistry·David C StiegRandy Strich

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Methods Mentioned

BETA
two hybrid
two-hybrid
Y2H
Co-immunoprecipitation
Fluorescence microscopy
PCR

Software Mentioned

IDR
GraphPad Prism
Image Pro
Mediator
NIS
ProteinPredict

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