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Mol Syst Biol

Title:		Positive roles for negative regulators in the mating response of yeast
Author(s):		Houser JR; Ford E; Nagiec MJ; Errede B; Elston TC;
Address:		"Department of Physics, University of North Carolina, Chapel Hill, NC 27599-7260, USA"
Journal Title:		Mol Syst Biol
Year:		2012
Volume:		20120605
Issue:
Page Number:		586 -
DOI:		10.1038/msb.2012.18
ISSN/ISBN:		1744-4292 (Electronic) 1744-4292 (Linking)
Abstract:		"All cells must detect and respond to changes in their environment, often through changes in gene expression. The yeast pheromone pathway has been extensively characterized, and is an ideal system for studying transcriptional regulation. Here we combine computational and experimental approaches to study transcriptional regulation mediated by Ste12, the key transcription factor in the pheromone response. Our mathematical model is able to explain multiple counterintuitive experimental results and led to several novel findings. First, we found that the transcriptional repressors Dig1 and Dig2 positively affect transcription by stabilizing Ste12. This stabilization through protein-protein interactions creates a large pool of Ste12 that is rapidly activated following pheromone stimulation. Second, we found that protein degradation follows saturating kinetics, explaining the long half-life of Ste12 in mutants expressing elevated amounts of Ste12. Finally, our model reveals a novel mechanism for robust perfect adaptation through protein-protein interactions that enhance complex stability. This mechanism allows the transcriptional response to act on a shorter time scale than upstream pathway activity"
Keywords:		"*Gene Expression Regulation, Fungal *Models, Biological Models, Genetic Mutation Pheromones/genetics/*metabolism Saccharomyces cerevisiae/*physiology Saccharomyces cerevisiae Proteins/genetics/*metabolism Transcription Factors/genetics/metabolism;"
Notes:		"MedlineHouser, John R Ford, Eintou Nagiec, Michal J Errede, Beverly Elston, Timothy C eng R01 GM073180/GM/NIGMS NIH HHS/ GM-073180/GM/NIGMS NIH HHS/ GM-079271/GM/NIGMS NIH HHS/ GM-084071/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural England 2012/06/07 Mol Syst Biol. 2012 Jun 5; 8:586. doi: 10.1038/msb.2012.18"