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Oxidative-stress-induced nuclear to cytoplasmic relocalization is required for Not4-dependent cyclin C destruction.

The yeast cyclin-C-Cdk8p kinase complex represses the transcription of a subset of genes involved in the stress response. To relieve this repression, cyclin C is destroyed in cells exposed to H(2)O(2) by the 26S proteasome. This report identifies Not4p as the ubiquitin ligase mediating H(2)O(2)-induced cyclin C destruction. Not4p is required for H(2)O(2)-induced cyclin C destruction in vivo and polyubiquitylates cyclin C in vitro by utilizing Lys48, a ubiquitin linkage associated with directing substrates to the 26S proteasome. Before its degradation, cyclin C, but not Cdk8p, translocates from the nucleus to the cytoplasm. This translocation requires both the cell-wall-integrity MAPK module and phospholipase C, and these signaling pathways are also required for cyclin C destruction. In addition, blocking cytoplasmic translocation slows the mRNA induction kinetics of two stress response genes repressed by cyclin C. Finally, a cyclin C derivative restricted to the cytoplasm is still subject to Not4p-dependent destruction, indicating that the degradation signal does not occur in the nucleus. These results identify a stress-induced proteolytic pathway regulating cyclin C that requires nuclear to cytoplasmic relocalization and Not4p-mediated ubiquitylation.

Pubmed ID: 22421358


  • Cooper KF
  • Scarnati MS
  • Krasley E
  • Mallory MJ
  • Jin C
  • Law MJ
  • Strich R


Journal of cell science

Publication Data

February 15, 2012

Associated Grants

  • Agency: NCI NIH HHS, Id: CA-099003
  • Agency: NIGMS NIH HHS, Id: GM086788

Mesh Terms

  • Cell Nucleolus
  • Cell Nucleus
  • Cell Wall
  • Cyclin C
  • Cyclin-Dependent Kinase 8
  • Cytoplasm
  • Gene Expression Regulation, Fungal
  • Hydrogen Peroxide
  • Mitogen-Activated Protein Kinases
  • Oxidative Stress
  • Protein Transport
  • Proteolysis
  • RNA, Fungal
  • RNA, Messenger
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Type C Phospholipases
  • Ubiquitin-Protein Ligases
  • Ubiquitination