Article

Fus3-triggered Tec1 degradation modulates mating transcriptional output during the pheromone response

Department of Biological Chemistry, University of California, Irvine, CA 92697, USA.
Molecular Systems Biology (Impact Factor: 14.1). 02/2008; 4:212. DOI: 10.1038/msb.2008.47
Source: PubMed

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.

0 Bookmarks
 · 
82 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: F-box proteins function in the recruitment of proteins for SCF ubiquitination and proteasome degradation. Here, we studied the role of Fbp1, a nonessential F-box protein of the tomato pathogen Fusarium oxysporum f. sp. lycopersici. The Δfbp1 mutant showed a significant delay in the production of wilt symptoms on tomato plants and was impaired in invasive growth on cellophane membranes and on living plant tissue. To search for target proteins recruited by Fbp1, a combination of sodium dodecylsulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) was used to compare proteins in mycelia of the wild-type and Δfbp1 mutant. The proteomic approach identified 41 proteins differing significantly in abundance between the two strains, 17 of which were more abundant in the Δfbp1 mutant, suggesting a possible regulation by proteasome degradation. Interestingly, several of the identified proteins were related to vesicle trafficking. Microscopic analysis revealed an impairment of the Δfbp1 strain in directional growth and in the structure of the Spitzenkörper, suggesting a role of Fbp1 in hyphal orientation. Our results indicate that Fbp1 regulates protein turnover and pathogenicity in F. oxysporum.
    Molecular Plant Pathology 07/2013; DOI:10.1111/mpp.12060 · 4.49 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Alkaline pH adaptation represents an important environmental stress response in Aspergillus nidulans. It is mediated by the pal signaling pathway and the PacC transcription factor. Although studied extensively experimentally, the activation mechanism of PacC has not been quantified, and it is not clear how this activation is regulated. Here, by constructing mathematical models, we first show that the pattern of PacC activation observed in previously published experiments cannot be explained based on existing knowledge about PacC activation. Extending the model with a negative feedback loop is necessary to produce simulation results that are consistent with the data, suggesting the existence of a negative feedback loop in the PacC activation process. This extended model is then validated against published measurements for cells with drug treatment and mutant cells. Furthermore, we investigate the role of an intermediate form of PacC in the PacC activation process, and propose experiments that can be used to test our predictions. Our work illustrates how mathematical models can be used to uncover regulatory mechanisms in the transcription regulation, and generate hypotheses that guide further laboratory investigations.
    Journal of Theoretical Biology 02/2013; DOI:10.1016/j.jtbi.2013.02.006 · 2.35 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The choice between alternative developmental pathways is primarily controlled at the level of transcription. Induction of meiosis in budding yeasts in response to nutrient levels provides a system to investigate the molecular basis of cellular decision-making. In Saccharomyces cerevisiae, entry into meiosis depends on multiple signals converging upon IME1, the master transcriptional activator of meiosis. Here we studied the regulation of the cis-acting regulatory element Upstream Activation Signal (UAS)ru, which resides within the IME1 promoter. Guided by our previous data acquired using a powerful high-throughput screening system, here we provide evidence that UASru is regulated by multiple stimuli that trigger distinct signal transduction pathways as follows: (i) The glucose signal inhibited UASru activity through the cyclic AMP (cAMP/protein kinase A (PKA) pathway, targeting the transcription factors (TFs), Com2 and Sko1; (ii) high osmolarity activated UASru through the Hog1/mitogen-activated protein kinase (MAPK) pathway and its corresponding TF Sko1; (iii) elevated temperature increased the activity of UASru through the cell wall integrity pathway and the TFs Swi4/Mpk1 and Swi4/Mlp1; (iv) the nitrogen source repressed UASru activity through Sum1; and (v) the absence of a nitrogen source was detected and transmitted to UASru by the Kss1 and Fus3 MAPK pathways through their respective downstream TFs, Ste12/Tec1 and Ste12/Ste12 as well as by their regulators Dig1/2. These signaling events were specific to UASru; they did not affect the mating and filamentation response elements that are regulated by MAPK pathways. The complex regulation of UASru through all the known vegetative MAPK pathways is unique to S. cerevisiae and is specific for IME1, likely because it is the master regulator of gametogenesis.
    PLoS ONE 11/2013; 8(11):e78920. DOI:10.1371/journal.pone.0078920 · 3.53 Impact Factor

Full-text (2 Sources)

Download
38 Downloads
Available from
Jun 2, 2014