TOR controls translation initiation and early G1 progression in yeast.
Saccharomyces cerevisiae cells treated with the immunosuppressant rapamycin or depleted for the targets of rapamycin TOR1 and TOR2 arrest growth in the early G1 phase of the cell cycle. Loss of TOR function also causes an early inhibition of translation initiation and induces several other physiological changes characteristic of starved cells entering stationary phase (G0). A G1 cyclin mRNA whose translational control is altered by substitution of the UBI4 5' leader region (UBI4 is normally translated under starvation conditions) suppresses the rapamycin-induced G1 arrest and confers starvation sensitivity. These results suggest that the block in translation initiation is a direct consequence of loss of TOR function and the cause of the G1 arrest. We propose that the TORs, two related phosphatidylinositol kinase homologues, are part of a novel signaling pathway that activates eIF-4E-dependent protein synthesis and, thereby, G1 progression in response to nutrient availability. Such a pathway may constitute a checkpoint that prevents early G1 progression and growth in the absence of nutrients.
Barbet
N C
NC
Department of Biochemistry, University of Basel, Switzerland.
Schneider
U
U
Helliwell
S B
SB
Stansfield
I
I
Tuite
M F
MF
Hall
M N
MN
D000935:Antifungal Agents / Q000494:pharmacology; D001483:Base Sequence; D015152:Blotting, Northern; D018797:Cell Cycle Proteins; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016193:G1 Phase; D015966:Gene Expression Regulation, Fungal; D008969:Molecular Sequence Data; D010442:Peptide Chain Initiation, Translational / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism / Q000502:physiology*; D010957:Plasmids; D011090:Polyenes / Q000494:pharmacology; D014176:Protein Biosynthesis; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction; D020123:Sirolimus
D000935:Antifungal Agents; D018797:Cell Cycle Proteins; D016213:Cyclins; D005656:Fungal Proteins; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011090:Polyenes; D029701:Saccharomyces cerevisiae Proteins; D020123:Sirolimus; C079895:CLN3 protein, S cerevisiae; C083324:TOR1 protein, S cerevisiae; C081135:TOR2 protein, S cerevisiae