The TOR signalling pathway controls nuclear localization of nutrient-regulated transcription factors.
The rapamycin-sensitive TOR signalling pathway in Saccharomyces cerevisiae activates a cell-growth program in response to nutrients such as nitrogen and carbon. The TOR1 and TOR2 kinases (TOR) control cytoplasmic protein synthesis and degradation through the conserved TAP42 protein. Upon phosphorylation by TOR, TAP42 binds and possibly inhibits type 2A and type-2A-related phosphatases; however, the mechanism by which TOR controls nuclear events such as global repression of starvation-specific transcription is unknown. Here we show that TOR prevents transcription of genes expressed upon nitrogen limitation by promoting the association of the GATA transcription factor GLN3 with the cytoplasmic protein URE2. The binding of GLN3 to URE2 requires TOR-dependent phosphorylation of GLN3. Phosphorylation and cytoplasmic retention of GLN3 are also dependent on the TOR effector TAP42, and are antagonized by the type-2A-related phosphatase SIT4. TOR inhibits expression of carbon-source-regulated genes by stimulating the binding of the transcriptional activators MSN2 and MSN4 to the cytoplasmic 14-3-3 protein BMH2. Thus, the TOR signalling pathway broadly controls nutrient metabolism by sequestering several transcription factors in the cytoplasm.
Beck
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Department of Biochemistry, Biozentrum, University of Basel, Switzerland.
Hall
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D048948:14-3-3 Proteins; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D029721:Drosophila Proteins; D005656:Fungal Proteins / Q000378:metabolism*; D050485:GABA Plasma Membrane Transport Proteins; D015966:Gene Expression Regulation, Fungal; D005979:Glutathione Peroxidase; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins; D009584:Nitrogen / Q000378:metabolism*; D027361:Organic Anion Transporters; D011328:Prions; D011506:Proteins / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D012097:Repressor Proteins; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase
D048948:14-3-3 Proteins; C097164:BMH2 protein, S cerevisiae; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D005656:Fungal Proteins; D050485:GABA Plasma Membrane Transport Proteins; C071664:GLN3 protein, S cerevisiae; C081935:MSN2 protein, S cerevisiae; C081937:MSN4 protein, S cerevisiae; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D027361:Organic Anion Transporters; D011328:Prions; D011506:Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C513599:UGA4 protein, S cerevisiae; D005979:Glutathione Peroxidase; C067020:URE2 protein, S cerevisiae; D014446:Tyrosine 3-Monooxygenase; D020794:Receptor Protein-Tyrosine Kinases; C080148:tor protein, Drosophila; D009584:Nitrogen