Abstract
Understanding how cell growth is regulated in response to environmental signals remains a challenging biological problem. Recent studies indicate the TOR (target of rapamycin) kinase acts within an intracellular regulatory network used by eukaryotic cells to regulate their growth according to nutrient availability. This network affects all aspects of gene expression, including transcription, translation, and protein stability, making TOR an excellent candidate as a global regulator of cellular activity. Here we review our recent studies of two specific transcriptional outputs controlled by TOR in the budding yeast, S. cerevisiae: (1) positive regulation of genes involved in ribosome biogenesis, and (2) negative regulation of genes required for de novo biosynthesis of glutamate and glutamine. These studies have raised the important issue as to how diverse nutritional cues can pass through a common signaling pathway and yet ultimately generate distinct transcriptional responses.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Beck, T. and M.N. Hall, The TOR signalling pathway controls nuclear localization of nutrient-regulated transcription factors. Nature, 1999. 402: p. 689–692
Cardenas, M.E., N.S. Cutler, M.C. Lorenz, C.J. Di Como, and J. Heitman, The TOR signaling cascade regulates gene expression in response to nutrients. Genes Dev., 1999. 13: p. 3271–3279
Chelstowska, A. and R.A. Butow, RTG genes in yeast that function in communication between mitochondria and the nucleus are also required for expression of genes encoding peroxisomal proteins. J. Biol. Chem., 1995. 270: p. 18141–18146
Courchesne, W.E. and B. Magasanik, Regulation of nitrogen assimilation in Saccharomyces cerevisiae: roles of the URE2 and GLN3 genes. J. Bacterid., 1988. 170: p. 708–713
Crespo, J.L., T. Powers, B. Fowler, and M.N. Hall, The TOR-controlled transcription activators GLN3, RTG1 and RTG3 are regulated in response to intracellular levels of glutamine. Proc. Natl. Acad. Sci. USA, 2002. in press
Dennis, P.B., S. Fumagalli, and G. Thomas, Target of rapamycin (TOR): balancing the opposing forces of protein synthesis and degradation. Curr. Opin. Genet. Dev., 1999. 9: p. 49–54
Dilova, I., C.-Y. Chen, and T. Powers, Mksl in concert with TOR signaling negatively regulates RTG target gene expression in S. cerevisiae. Curr. Biol., 2002. 12: p. 389–395
Epstein, C.B., J.A. Waddle, W. Hale, V. Dave, J. Thornton, T.L. Macatee, H.R. Garner, and R.A. Butow, Genome-wide responses to mitochondria dysfunction. Mol. Biol. Cell, 2001. 12: p. 297–308
Hardwick, J.S., EG. Kuruvilla, J.K. Tong, A.E Shamji, and S.L. Schreiber, Rapamycin-modulated transcription defines the subset of nutrient-sensitive signaling pathways directly controlled by the Tor proteins. Proc. Natl. Acad. Sci. USA, 1999. 96: p. 14866–14870
Jefferies, H.B.J., S. Fumagalli, P.B. Dennis, C. Reinhard, R.B. Pearson, and G. Thomas, Rapamycin suppresses 5′TOP mRNA translation through inhibition of p70s6k. EMBO J., 1997. 16(12): p. 3693–3704
Jefferies, H.B.J, and G. Thomas, Ribosomal protein S6 phosphorylation and signal transduction, in Translational Control, J.W.B. Hershey, M.B. Mathews, and N. Sonenberg, Editors. 1996, Cold Spring Harbor Laboratory Press: Cold Spring Harbor, NY. p. 389–409
Johnson, S.P. and J.R. Warner, Phosphorylation of the Saccharomyces cerevisiae equivalent of ribosomal protein S6 has no detectable effect on growth. Mol. Cell. Biol., 1987. 7: p. 1338–1345
Komeili, A., K.P. Wedaman, E.O. O’Shea, and T. Powers, Mechanism of metabolic control: Target of rapamycin signaling links nitrogen quality to the activity of the Rtgl and Rtg3 transcription factors. J. Cell Biol., 2000. 151: p. 863–878
Kos, W., A.J. Kal, S. van Wilpe, and H.R Tabak, Expression of genes encoding peroxisomal proteins in Saccharomyces cerevisiae is regulated by different circuits of transcriptional control. Biochim. Biophys. Acta, 1995. 1264: p. 79–86
Kovacevic, Z. and J.D. McGivan, Mitochondrial metabolism of glutamine and gluta-mate and its physiological significance. Phys. Rev., 1983. 63: p. 547–605
Leicht, M., A. Simm, G. Bertsch, and J. Hoppe, Okadaic acid induces cellular hypertrophy in AKR-2B fibroblasts: involvement of the p70S6 kinase in the onset of protein and rRNA synthesis. Cell Growth Differ., 1996. 7: p. 1199–1209
Liao, X. and R.A. Butow, RTG1 and RTG2: two yeast genes required for a novel path of communication from mitochondria to the nucleus. Cell, 1993. 72: p. 61–71
Liao, X., W.C. Small, P.A. Srere, and R.A. Butow, Intramitochondrial functions regulate nonmitochondrial citrate synthase (CIT2) expression in Saccharomyces cerevisiae. Mol. Cell. Biol., 1991. 11: p. 38–46
Liu, Z. and R.A. Butow, A transcriptional switch in the expression of yeast tricarboxylic acid cycle genes in response to a reduction or loss of respiratory function. Mol. Cell. Biol., 1999. 19: p. 6720–6728
Mahajan, P.B., Modulation of transcription of rRNA genes by rapamycin. Int. J. Im-munopharmacol., 1994. 16: p. 711–21
McCammon, M.T., Mutants of Saccharomyces cerevisiae with defects in acetate metabolism: isolation and characterization of Acn- mutants. Genetics, 1996. 144: p. 57–69
Powers, T. and P. Walter, Regulation of ribosome biogenesis by the rapamycin-sensitive TOR-signaling pathway in Saccharomyces cerevisiae. Mol. Biol. Cell, 1999. 10: p. 987–1000
Rohde, J., J. Heitman, and M.E. Cardenas, The TOR kinases link nutrient sensing to cell growth. J. Biol. Chem., 2001. 276: p. 9583–9586
Schmelzle, T. and M.N. Hall, TOR, a central controller of cell growth. Cell, 2000. 103: p. 253–262
Sekito, T, Z. Liu, J. Thornton, and R.A. Butow, RTG-dependent mitochondria-to-nu-cleus signaling is regulated by Mks1 and is linked to formation of yeast prion [URE3]. Mol. Biol. Cell, 2002. 13: p. 795–804
Sekito, T, J. Thorton, and R. Butow, Mitochondria-to-nuclear signaling is regulated by the subcellular localization of the transcription factors Rtg1p and Rtg3p. Mol. Biol. Cell, 2000. 11: p. 2103–2115
Shamji, A.E, EG. Kuruvilla, and S.L. Schreiber, Partitioning the transcriptional program induced by rapmycin among the effectors of the Tor proteins. Curr. Biol., 2000. 10: p. 1574–1581
Thomas, G. and M.N. Hall, TOR signalling and control of cell growth. Curr. Opin. Cell Biol., 1997. 9: p. 782–787
Warner, J.R., The economics of ribosome biosynthesis in yeast. Trends Biochem. Sci., 1999. 24: p. 437–440
Woolford, J.L., Jr. and J.R. Warner, The ribosome and its synthesis, in The molecular biology and cellular biology of the yeast Saccharomyces cerevisiae, J.R. Broach, J.R. Pringle, and E.W. Jones, Editors. 1991, Cold Spring Harbor Laboratory Press: Cold Spring Harbor, NY. p. 587–626
Zaragoza, D., A. Ghavidel, J. Heitman, and M.C. Schultz, Rapamycin induces the G0 program of transcriptional repression in yeast by interfering with the TOR signaling pathway. Mol. Cell. Biol., 1998. 18: p. 4463–4470
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2004 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Powers, T., Dilova, I., Chen, CY., Wedaman, K. (2004). Yeast TOR Signaling: A Mechanism for Metabolic Regulation. In: Thomas, G., Sabatini, D.M., Hall, M.N. (eds) TOR. Current Topics in Microbiology and Immunology, vol 279. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-18930-2_3
Download citation
DOI: https://doi.org/10.1007/978-3-642-18930-2_3
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-62360-8
Online ISBN: 978-3-642-18930-2
eBook Packages: Springer Book Archive