title: Degradation of the Saccharomyces cerevisiae mating-type regulator alpha1: genetic dissection of cis-determinants and trans-acting pathways.
abstract: Mating phenotype in the yeast Saccharomyces cerevisiae is a dynamic trait, and efficient transitions between alternate haploid cell types allow the organism to access the advantageous diploid form. Mating identity is determined by cell type-specific transcriptional regulators, but these factors must be rapidly removed upon mating-type switching to allow the master regulators of the alternate state to establish a new gene expression program. Targeted proteolysis by the ubiquitin-proteasome system is a commonly employed strategy to quickly disassemble regulatory networks, and yeast use this approach to evoke efficient switching from the alpha to the a phenotype by ensuring the rapid removal of the alpha2 transcriptional repressor. Transition to the a cell phenotype, however, also requires the inactivation of the alpha1 transcriptional activator, but the mechanism by which this occurs is currently unknown. Here, we report a central role for the ubiquitin-proteasome system in alpha1 inactivation. The alpha1 protein is constitutively short lived and targeted for rapid turnover by multiple ubiquitin-conjugation pathways. Intriguingly, the alpha-domain, a conserved region of unknown function, acts as a degradation signal for a pathway defined by the SUMO-targeted ligase Slx5-Slx8, which has also been implicated in the rapid destruction of alpha2. Our observations suggest coordinate regulation in the turnover of two master regulatory transcription factors ensures a rapid mating-type switch.
authors.affiliation: Department of Molecular Biology, Brown University, Providence, Rhode Island 02912, USA.
authors.forename: Christina E
authors.initials: CE
authors.lastname: Nixon
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Wilcox
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Laney
mesh_terms: D008025:Ligases / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism
chemical_list: D011506:Proteins; D014157:Transcription Factors; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex; D008025:Ligases