TY - JOUR
T1 - Degradation of the Saccharomyces cerevisiae mating-type regulator α1
T2 - Genetic dissection of Cis-determinants and trans-acting pathways
AU - Nixon, Christina E.
AU - Wilcox, Alexander J.
AU - Laney, Jeffrey D.
PY - 2010/6
Y1 - 2010/6
N2 - 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 α to the a phenotype by ensuring the rapid removal of the α2 transcriptional repressor. Transition to the a cell phenotype, however, also requires the inactivation of the α1 transcriptional activator, but the mechanism by which this occurs is currently unknown. Here, we report a central role for the ubiquitin-proteasome system in α1 inactivation. The α1 protein is constitutively short lived and targeted for rapid turnover by multiple ubiquitin-conjugation pathways. Intriguingly, the α-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 α2. Our observations suggest coordinate regulation in the turnover of two master regulatory transcription factors ensures a rapid mating-type switch.
AB - 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 α to the a phenotype by ensuring the rapid removal of the α2 transcriptional repressor. Transition to the a cell phenotype, however, also requires the inactivation of the α1 transcriptional activator, but the mechanism by which this occurs is currently unknown. Here, we report a central role for the ubiquitin-proteasome system in α1 inactivation. The α1 protein is constitutively short lived and targeted for rapid turnover by multiple ubiquitin-conjugation pathways. Intriguingly, the α-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 α2. Our observations suggest coordinate regulation in the turnover of two master regulatory transcription factors ensures a rapid mating-type switch.
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U2 - 10.1534/genetics.110.115907
DO - 10.1534/genetics.110.115907
M3 - Article
C2 - 20351217
AN - SCOPUS:77955485845
SN - 0016-6731
VL - 185
SP - 497
EP - 511
JO - Genetics
JF - Genetics
IS - 2
ER -