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Rowan University

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Med13

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Snf1 Cooperates With The Cwi Mapk Pathway To Mediate The Degradation Of Med13 Following Oxidative Stress, Stephen D Willis, David C Stieg, Kai Li Ong, Ravina Shah, Alexandra K. Strich, Julianne H Grose, Katrina F Cooper Jun 2018

Snf1 Cooperates With The Cwi Mapk Pathway To Mediate The Degradation Of Med13 Following Oxidative Stress, Stephen D Willis, David C Stieg, Kai Li Ong, Ravina Shah, Alexandra K. Strich, Julianne H Grose, Katrina F Cooper

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

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 …


Snf1 Dependent Destruction Of Med13 Is Required For Programmed Cell Death Following Oxidative Stress In Yeast, Stephen D Willis, David C Stieg, R. Shah, Randy Strich, Katrina F Cooper Dec 2017

Snf1 Dependent Destruction Of Med13 Is Required For Programmed Cell Death Following Oxidative Stress In Yeast, Stephen D Willis, David C Stieg, R. Shah, Randy Strich, Katrina F Cooper

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

All eukaryotic cells, when faced with unfavorable environmental conditions, have to decide whether to mount a survival or cell death response. The conserved cyclin C and its kinase partner Cdk8 play 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 S. cerevisiae, oxidative stress triggers Med13 destruction1, which thereafter releases cyclin Ci nto the cytoplasm. Cytoplasmic cyclin C associates with mitochondria where it induces hyper-fragmentation and programmed cell death2. This suggests a model in …


The Role Of Mapk And Scf In The Destruction Of Med13 In Cyclin C Mediated Cell Death, David C Stieg, Stephen D Willis, Joseph Scuorzo, Mia Song, Vidyaramanan Ganesan, Randy Strich, Katrina F Cooper Dec 2017

The Role Of Mapk And Scf In The Destruction Of Med13 In Cyclin C Mediated Cell Death, David C Stieg, Stephen D Willis, Joseph Scuorzo, Mia Song, Vidyaramanan Ganesan, Randy Strich, Katrina F Cooper

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

In response to stress, the yeast1 and mammalian2 cyclin C translocate from the nucleus to the cytoplasm, where it associates with the GTPase Drp1/Dnm1 to drive mitochondrial fragmentation and apoptosis. Therefore, the decision to release cyclin C represents a key life or death decision. In unstressed cells, the cyclin C‐Cdk8 kinase regulates transcription by associating with the Mediator of RNA polymerase II. We previously reported that the Mediator component Med13 anchors cyclin C in the nucleus3. Loss of Med13 function leads to constitutive cytoplasmic localization of cyclin C, resulting in fragmented mitochondria, hypersensitivity to stress and …