Slt2p phosphorylation induces cyclin C nuclear-to-cytoplasmic translocation in response to oxidative stress

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30 Scopus citations

Abstract

The yeast C-type cyclin represses the transcription of genes required for the stress response and meiosis. To relieve this repression, cyclin C undergoes nuclear-to-cytoplasmic translocation in response to many stressors, including hydrogen peroxide, where it is destroyed by ubiquitin-mediated proteolysis. Before its destruction, cyclin C promotes stress-induced mitochondrial fission and programmed cell death, indicating that relocalization is an important cell fate regulator. Here we show that cyclin C cytoplasmic translocation requires the cell wall integrity (CWI) mitogen-activated protein kinase Slt2p, its pseudokinase paralogue, Kdx1p, and an associating transcription factor, Ask10p. Furthermore, Slt2p and Kdx1p regulate cyclin C stability through different but required mechanisms. Slt2p associates with, and directly phosphorylates, cyclin C at Ser-266. Eliminating or mimicking phosphorylation at this site restricts or enhances cyclin C cytoplasmic translocation and degradation, respectively. Conversely, Kdx1p does not bind cyclin C but instead coimmunoprecipitates with Ask10p, a transcription factor previously identified as a regulator of cyclin C destruction. These results reveal a complex regulatory circuitry involving both downstream effectors of the CWI mitogen-activated protein kinase signal transduction pathway to target the relocalization and consequent destruction of a single transcriptional repressor.

Original languageEnglish (US)
Pages (from-to)1396-1407
Number of pages12
JournalMolecular biology of the cell
Volume25
Issue number8
DOIs
StatePublished - Apr 15 2014

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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