title: Pheromone-induced degradation of Ste12 contributes to signal attenuation and the specificity of developmental fate.
abstract: The Ste12 transcription factor of Saccharomyces cerevisiae regulates transcription programs controlling two different developmental fates. One is differentiation into a mating-competent form that occurs in response to mating pheromone. The other is the transition to a filamentous-growth form that occurs in response to nutrient deprivation. These two distinct roles for Ste12 make it a focus for studies into regulatory mechanisms that impart biological specificity. The transient signal characteristic of mating differentiation led us to test the hypothesis that regulation of Ste12 turnover might contribute to attenuation of the mating-specific transcription program and restrict activation of the filamentation program. We show that prolonged pheromone induction leads to ubiquitin-mediated destabilization and decreased amounts of Ste12. This depletion in pheromone-stimulated cultures is dependent on the mating-pathway-dedicated mitogen-activated protein kinase Fus3 and its target Cdc28 inhibitor, Far1. Attenuation of pheromone-induced mating-specific gene transcription (FUS1) temporally correlates with Ste12 depletion. This attenuation is abrogated in the deletion backgrounds (fus3Delta or far1Delta) where Ste12 is found to persist. Additionally, pheromone induces haploid invasion and filamentous-like growth instead of mating differentiation when Ste12 levels remain high. These observations indicate that loss of Ste12 reinforces the adaptive response to pheromone and contributes to the curtailing of a filamentation response.
authors.affiliation: Department of Biochemistry and Biophysics, CB 7260 512 ME Jones, University of North Carolina, Chapel Hill, NC 27599-7260, USA.
authors.forename: R Keith
authors.initials: RK
authors.lastname: Esch
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Wang
authors.forename: Beverly
authors.initials: B
authors.lastname: Errede
mesh_terms: D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D004271:DNA, Fungal / Q000235:genetics; D005800:Genes, Fungal; D006238:Haploidy; D000072235:Mating Factor; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D004271:DNA, Fungal; C081353:FAR1 protein, S cerevisiae; D010455:Peptides; D012097:Repressor Proteins; C489241:STE12 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D025801:Ubiquitin; D000072235:Mating Factor; C075580:FUS3 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases