title: Slt2p phosphorylation induces cyclin C nuclear-to-cytoplasmic translocation in response to oxidative stress.
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.
authors.affiliation: Department of Molecular Biology, Rowan University School of Osteopathic Medicine, Stratford, NJ 08084.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Jin
authors.forename: Randy
authors.initials: R
authors.lastname: Strich
authors.forename: Katrina F
authors.initials: KF
authors.lastname: Cooper
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001426:Bacterial Proteins; D056745:Cyclin C / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology; D047468:Immunoprecipitation; D008164:Luminescent Proteins; D020935:MAP Kinase Signaling System; D008928:Mitochondria / Q000378:metabolism; D063154:Mitochondrial Dynamics / Q000187:drug effects*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D018384:Oxidative Stress; D010766:Phosphorylation; D021381:Protein Transport; D016601:RNA-Binding Proteins; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C487632:Ask10 protein, S cerevisiae; D001426:Bacterial Proteins; D056745:Cyclin C; D008164:Luminescent Proteins; C080988:MLP1 protein, S cerevisiae; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C054562:yellow fluorescent protein, Bacteria; D006861:Hydrogen Peroxide; D020928:Mitogen-Activated Protein Kinases; C072724:SLT2 protein, S cerevisiae