Ubiquitin–proteasome-mediated cyclin C degradation promotes cell survival following nitrogen starvation

Stephen D. Willis, Sara E. Hanley, Thomas Beishke, Prasanna D. Tati, Katrina F. Cooper

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Environmental stress elicits well-orchestrated programs that either restore cellular homeostasis or induce cell death depending on the insult. Nutrient starvation triggers the autophagic pathway that requires the induction of several Autophagy (ATG) genes. Cyclin C–cyclin-dependent kinase (Cdk8) is a component of the RNA polymerase II Mediator complex that predominantly represses the transcription of stress-responsive genes in yeast. To relieve this repression following oxidative stress, cyclin C translocates to the mitochondria where it induces organelle fragmentation and promotes cell death prior to its destruction by the ubiquitin–proteasome system (UPS). Here we report that cyclin C-Cdk8, together with the Ume6-Rpd3 histone deacetylase complex, represses the essential autophagy gene ATG8. Similar to oxidative stress, cyclin C is destroyed by the UPS following nitrogen starvation. Removing this repression is important as deleting CNC1 allows enhanced cell growth under mild starvation. However, unlike oxidative stress, cyclin C is destroyed prior to its cytoplasmic translocation. This is important as targeting cyclin C to the mitochondria induces both mitochondrial fragmentation and cell death following nitrogen starvation. These results indicate that cyclin C destruction pathways are fine tuned depending on the stress and that its terminal subcellular address influences the decision between initiating cell death or cell survival pathways.

Original languageEnglish (US)
Pages (from-to)1015-1031
Number of pages17
JournalMolecular biology of the cell
Issue number10
StatePublished - May 2020

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology


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