Title: | Fus3-triggered Tec1 degradation modulates mating transcriptional output during the pheromone response |
Author(s): | Chou S; Zhao S; Song Y; Liu H; Nie Q; |
Address: | "Department of Biological Chemistry, University of California, Irvine, CA 92697, USA" |
ISSN/ISBN: | 1744-4292 (Electronic) 1744-4292 (Linking) |
Abstract: | "The yeast transcription factor Ste12 controls both mating and filamentation pathways. Upon pheromone induction, the mitogen-activated protein kinases, Fus3 and Kss1, activate Ste12 by relieving the repression of two functionally redundant Ste12 inhibitors, Dig1 and Dig2. Mating genes are controlled by the Ste12/Dig1/Dig2 complex through Ste12-binding sites, whereas filamentation genes are regulated by the Tec1/Ste12/Dig1 complex through Tec1-binding sites. The two Ste12 complexes are mutually exclusive. During pheromone response, Tec1 is degraded upon phosphorylation by Fus3, preventing cross-activation of the filamentation pathway. Here, we show that a stable Tec1 also impairs the induction of mating genes. A mathematical model is developed to capture the dynamic formation of the two Ste12 complexes and their interactions with pathway-specific promoters. By model simulations and experimentation, we show that excess Tec1 can impair the mating transcriptional output because of its ability to sequester Ste12, and because of a novel function of Dig2 for the transcription of mating genes. We suggest that Fus3-triggered Tec1 degradation is an important part of the transcriptional induction of mating genes during the pheromone response" |
Keywords: | "Computer Simulation DNA-Binding Proteins/genetics/*metabolism *Gene Expression Regulation, Fungal Mitogen-Activated Protein Kinases/genetics/*metabolism Models, Genetic Mutation Phosphorylation Promoter Regions, Genetic Reproduction Saccharomyces cerevisi;" |
Notes: | "MedlineChou, Song Zhao, Su Song, You Liu, Haoping Nie, Qing eng R01GM67247/GM/NIGMS NIH HHS/ R01 GM067247/GM/NIGMS NIH HHS/ P50GM76516/GM/NIGMS NIH HHS/ P50 GM076516/GM/NIGMS NIH HHS/ R01GM/AI55155/AI/NIAID NIH HHS/ R01GM75309/GM/NIGMS NIH HHS/ R01 GM075309/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England 2008/08/07 Mol Syst Biol. 2008; 4:212. doi: 10.1038/msb.2008.47. Epub 2008 Aug 5" |