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

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. Prior to 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 paralog 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 Ser266. 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 rather 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 MAPK signal transduction pathway to target the relocalization and consequent destruction of a single transcriptional repressor.
Mol. Biol. Cell
Date: Feb. 19, 2014
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