Houser2012_pheromone_Ste12
This model is from the article:
Positive roles for negative regulators in the mating response of yeast.
Houser JR, Ford E, Nagiec MJ, Errede B, Elston TC. Mol Syst Biol
2012 June 5;8:586 22669614
,
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.
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Positive roles for negative regulators in the mating response of yeast.
- Houser JR, Ford E, Nagiec MJ, Errede B, Elston TC
- Molecular Systems Biology , 6/ 2012 , Volume 8 , pages: 586 , PubMed ID: 22669614
- Department of Physics, University of North Carolina, Chapel Hill, NC 27599-7260, USA.
- 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.
Submitter of this revision: John Houser
Modellers: John Houser
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| MODEL1204040000_url.xml | SBML L2V4 representation of Houser2012_pheromone_Ste12 | 65.98 KB | Preview | Download |
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| MODEL1204040000-biopax2.owl | Auto-generated BioPAX (Level 2) | 50.23 KB | Preview | Download |
| MODEL1204040000-biopax3.owl | Auto-generated BioPAX (Level 3) | 83.08 KB | Preview | Download |
| MODEL1204040000.m | Auto-generated Octave file | 12.97 KB | Preview | Download |
| MODEL1204040000.pdf | Auto-generated PDF file | 281.96 KB | Preview | Download |
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| MODEL1204040000.vcml | Auto-generated VCML file | 43.87 KB | Preview | Download |
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- Model originally submitted by : John Houser
- Submitted: Apr 4, 2012 9:20:21 PM
- Last Modified: Jul 30, 2012 2:58:37 PM
Revisions
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Version: 2
- Submitted on: Jul 30, 2012 2:58:37 PM
- Submitted by: John Houser
- With comment: Current version of Houser2012_pheromone_Ste12
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Version: 1
- Submitted on: Apr 4, 2012 9:20:21 PM
- Submitted by: John Houser
- With comment: Original import of Houser2012_pheromone_Ste12
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