Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
    Mol Syst Biol. 2012 Jun 5;8:586. doi: 10.1038/msb.2012.18.

    Positive roles for negative regulators in the mating response of yeast.

    Source

    Department of Physics, University of North Carolina, Chapel Hill, NC 27599-7260, USA.

    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.

    PMID:
    22669614
    [PubMed - indexed for MEDLINE]
    PMCID:
    PMC3397415
    Free PMC Article

    Images from this publication.See all images (7)Free text

    Figure 1
    Figure 3
    Figure 5
    Figure 7
    Figure 2
    Figure 4
    Figure 6

      Supplemental Content

      Icon for Nature Publishing Group Icon for PubMed Central

      Save items

      Recent activity

      Your browsing activity is empty.

      Activity recording is turned off.

      Turn recording back on

      See more...
      Write to the Help Desk