TOR and PKA pathways synergize at the level of the Ste11 transcription factor to prevent mating and meiosis in fission yeast.
BACKGROUND
In the fission yeast Schizosaccharomyces pombe, the TOR (target of rapamycin) and PKA (protein kinase A) signaling transduction pathways regulate the expression of genes required for cell growth and sexual differentiation in response to the nutritional environment. Inhibition of Tor2 signaling results in the induction of genes involved in sexual differentiation, and the cells undergo mating and meiosis, even under good nutritional conditions. The same phenotype is observed in mutants in which the PKA pathway is inactive. By contrast, Tor2 overexpression or mutations that hyperactivate PKA signaling impair sexual differentiation, even under poor nutritional conditions. Accordingly, a very important question is to understand the molecular mechanism by which these two pathways coordinately regulate gene expression in response to nutrients.


RESULTS
Here we demonstrate that TOR and PKA pathways operate coordinately to negatively regulate sexual differentiation by inhibiting the nuclear accumulation of the Ste11 transcription factor. However, the Tor2 pathway is unable to block the nuclear localization of Ste11 under good nutritional conditions when the PKA pathway is inactive. Using microarray analyses, we found that both pathways inhibit sexual differentiation by blocking ste11-dependent gene expression.


CONCLUSIONS
We conclude that both the PKA and the TOR pathways inhibit Ste11 nuclear accumulation to repress Ste11-dependent gene expression. However, the PKA pathway plays a quantitatively more important role than the TOR pathway in this process.
Valbuena
Noelia
N
Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas, Salamanca University, Salamanca, Spain.
Moreno
Sergio
S
D015152:Blotting, Northern; D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D015966:Gene Expression Regulation, Fungal / Q000235:genetics / Q000502:physiology; D008540:Meiosis / Q000235:genetics / Q000502:physiology*; D008856:Microscopy, Fluorescence; D020411:Oligonucleotide Array Sequence Analysis; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; C071596:ste11 protein, S pombe; D011494:Protein Kinases; D017868:Cyclic AMP-Dependent Protein Kinases