Rapamycin-modulated transcription defines the subset of nutrient-sensitivesignaling pathways directly controlled by the Tor proteins

The immunosuppressant rapamycin inhibits Tor1p and Tor2p (target of rapamyc in proteins), ultimately resulting in cellular responses characteristic of nutrient deprivation through a mechanism involving translational arrest. We measured the immediate transcriptional response of yeast grown in rich med ia and treated with rapamycin to investigate the direct effects of Tor prot eins on nutrient-sensitive signaling pathways. The results suggest that Tor proteins directly modulate the glucose activation and nitrogen discriminat ion pathways and the pathways that respond to the diauxic shift (including glycolysis and the citric acid cycle). Tor proteins do not directly modulat e the general amino acid control, nitrogen starvation, or sporulation (in d iploid cells) pathways. Poor nitrogen quality activates the nitrogen discri mination pathway, which is controlled by the complex of the transcriptional repressor Ure2p and activator Gln3p. Inhibiting Tor proteins with rapamyci n increases the electrophoretic mobility of Ure2p. The work presented here illustrates the coordinated use of genome-based and biochemical approaches to delineate a cellular pathway modulated by the protein target of a small molecule.