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NC Barbet, U Schneider, SB Helliwell, I Stansfield, MF Tuite and MN Hall
Department of Biochemistry, University of Basel, Switzerland.
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.
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N. S. Cutler, X. Pan, J. Heitman, and M. E. Cardenas The TOR Signal Transduction Cascade Controls Cellular Differentiation in Response to Nutrients Mol. Biol. Cell, December 1, 2001; 12(12): 4103 - 4113. [Abstract] [Full Text] [PDF]
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K. E. Hentges, B. Sirry, A.-C. Gingeras, D. Sarbassov, N. Sonenberg, D. Sabatini, and A. S. Peterson FRAP/mTOR is required for proliferation and patterning during embryonic development in the mouse PNAS, November 9, 2001; (2001) 241184198. [Abstract] [Full Text] [PDF]
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 M. C. Cruz, A. L. Goldstein, J. Blankenship, M. Del Poeta, J. R. Perfect, J. H. McCusker, Y. L. Bennani, M. E. Cardenas, and J. Heitman Rapamycin and Less Immunosuppressive Analogs Are Toxic to Candida albicans and Cryptococcus neoformans via FKBP12-Dependent Inhibition of TOR Antimicrob. Agents Chemother., November 1, 2001; 45(11): 3162 - 3170. [Abstract] [Full Text] [PDF]
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A. R. Albig and C. J. Decker The Target of Rapamycin Signaling Pathway Regulates mRNA Turnover in the Yeast Saccharomyces cerevisiae Mol. Biol. Cell, November 1, 2001; 12(11): 3428 - 3438. [Abstract] [Full Text] [PDF]
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 M. Miron and N. Sonenberg Regulation of Translation via TOR Signaling: Insights from Drosophila melanogaster J. Nutr., November 1, 2001; 131(11): 2988S - 2993. [Abstract] [Full Text] [PDF]
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H. Abeliovich and D. J. Klionsky Autophagy in Yeast: Mechanistic Insights and Physiological Function Microbiol. Mol. Biol. Rev., September 1, 2001; 65(3): 463 - 479. [Abstract] [Full Text] [PDF]
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L. S. Jefferson and S. R. Kimball Amino Acid Regulation of Gene Expression J. Nutr., September 1, 2001; 131(9): 2460S - 2466. [Abstract] [Full Text] [PDF]
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 I. Paz and M. Choder Eukaryotic Translation Initiation Factor 4E-Dependent Translation Is Not Essential for Survival of Starved Yeast Cells J. Bacteriol., August 1, 2001; 183(15): 4477 - 4483. [Abstract] [Full Text] [PDF]
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B. Raught, A.-C. Gingras, and N. Sonenberg The target of rapamycin (TOR) proteins PNAS, June 19, 2001; 98(13): 7037 - 7044. [Abstract] [Full Text] [PDF]
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F. G. Kuruvilla, A. F. Shamji, and S. L. Schreiber Carbon- and nitrogen-quality signaling to translation are mediated by distinct GATA-type transcription factors PNAS, June 19, 2001; 98(13): 7283 - 7288. [Abstract] [Full Text] [PDF]
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G. J. Smits, H. van den Ende, and F. M. Klis Differential regulation of cell wall biogenesis during growth and development in yeast Microbiology, April 1, 2001; 147(4): 781 - 794. [Full Text]
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A.-C. Gingras, B. Raught, and N. Sonenberg Regulation of translation initiation by FRAP/mTOR Genes & Dev., April 1, 2001; 15(7): 807 - 826. [Full Text]
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 H. Abeliovich, W. A. Dunn Jr., J. Kim, and D. J. Klionsky Dissection of Autophagosome Biogenesis into Distinct Nucleation and Expansion Steps J. Cell Biol., November 27, 2000; 151(5): 1025 - 1034. [Abstract] [Full Text] [PDF]
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A. Komeili, K. P. Wedaman, E. K. O'Shea, and T. Powers Mechanism of Metabolic Control: Target of Rapamycin Signaling Links Nitrogen Quality to the Activity of the Rtg1 and Rtg3 Transcription Factors J. Cell Biol., November 13, 2000; 151(4): 863 - 878. [Abstract] [Full Text] [PDF]
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F. Abe and K. Horikoshi Tryptophan Permease Gene TAT2 Confers High-Pressure Growth in Saccharomyces cerevisiae Mol. Cell. Biol., November 1, 2000; 20(21): 8093 - 8102. [Abstract] [Full Text]
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S. R. Kimball, L. S. Jefferson, H. V. Nguyen, A. Suryawan, J. A. Bush, and T. A. Davis Feeding stimulates protein synthesis in muscle and liver of neonatal pigs through an mTOR-dependent process Am J Physiol Endocrinol Metab, November 1, 2000; 279(5): E1080 - E1087. [Abstract] [Full Text] [PDF]
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S. Oldham, J. Montagne, T. Radimerski, G. Thomas, and E. Hafen Genetic and biochemical characterization of dTOR, the Drosophila homolog of the target of rapamycin Genes & Dev., November 1, 2000; 14(21): 2689 - 2694. [Abstract] [Full Text]
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H. Zhang, J. P. Stallock, J. C. Ng, C. Reinhard, and T. P. Neufeld Regulation of cellular growth by the Drosophila target of rapamycin dTOR Genes & Dev., November 1, 2000; 14(21): 2712 - 2724. [Abstract] [Full Text]
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O. J. Shah, J. C. Anthony, S. R. Kimball, and L. S. Jefferson 4E-BP1 and S6K1: translational integration sites for nutritional and hormonal information in muscle Am J Physiol Endocrinol Metab, October 1, 2000; 279(4): E715 - E729. [Abstract] [Full Text] [PDF]
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G. P. Cosentino, T. Schmelzle, A. Haghighat, S. B. Helliwell, M. N. Hall, and N. Sonenberg Eap1p, a Novel Eukaryotic Translation Initiation Factor 4E-Associated Protein in Saccharomyces cerevisiae Mol. Cell. Biol., July 1, 2000; 20(13): 4604 - 4613. [Abstract] [Full Text]
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J. T. Brown, X. Yang, and A. W. Johnson Inhibition of mRNA Turnover in Yeast by an xrn1 Mutation Enhances the Requirement for eIF4E Binding to eIF4G and for Proper Capping of Transcripts by Ceg1p Genetics, May 1, 2000; 155(1): 31 - 42. [Abstract] [Full Text]
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B. K. Law, P. Norgaard, and H. L. Moses Farnesyltransferase Inhibitor Induces Rapid Growth Arrest and Blocks p70s6k Activation by Multiple Stimuli J. Biol. Chem., April 6, 2000; 275(15): 10796 - 10801. [Abstract] [Full Text] [PDF]
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R. T. Peterson, P. A. Beal, M. J. Comb, and S. L. Schreiber FKBP12-Rapamycin-associated Protein (FRAP) Autophosphorylates at Serine 2481 under Translationally Repressive Conditions J. Biol. Chem., March 15, 2000; 275(10): 7416 - 7423. [Abstract] [Full Text] [PDF]
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M. P. Ashe, S. K. De Long, and A. B. Sachs Glucose Depletion Rapidly Inhibits Translation Initiation in Yeast Mol. Biol. Cell, March 1, 2000; 11(3): 833 - 848. [Abstract] [Full Text]
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