This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zaragoza, D.
Right arrow Articles by Schultz, M. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zaragoza, D.
Right arrow Articles by Schultz, M. C.

 Previous Article  |  Next Article 

Mol Cell Biol, August 1998, p. 4463-4470, Vol. 18, No. 8
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Rapamycin Induces the G0 Program of Transcriptional Repression in Yeast by Interfering with the TOR Signaling Pathway

Dean Zaragoza,1 Ataollah Ghavidel,1 Joseph Heitman,2 and Michael C. Schultz1 *

Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2H7,1 and Departments of Genetics and Pharmacology, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 277102

Received 2 April 1998/Returned for modification 7 May 1998/Accepted 13 May 1998

The macrolide antibiotic rapamycin inhibits cellular proliferation by interfering with the highly conserved TOR (for target of rapamycin) signaling pathway. Growth arrest of budding yeast cells treated with rapamycin is followed by the program of molecular events that characterizes entry into G0 (stationary phase), including the induction of polymerase (Pol) II genes typically expressed only in G0. Normally, progression into G0 is characterized by transcriptional repression of the Pol I and III genes. Here, we show that rapamycin treatment also causes the transcriptional repression of Pol I and III genes. The down-regulation of Pol III transcription is TOR dependent. While it coincides with translational repression by rapamycin, transcriptional repression is due in part to a translation-independent effect that is evident in extracts from a conditional tor2 mutant. Biochemical experiments reveal that RNA Pol III and probably transcription initiation factor TFIIIB are targets of repression by rapamycin. In view of previous evidence that TFIIIB and Pol III are inhibited when protein phosphatase 2A (PP2A) function is impaired, and that PP2A is a component of the TOR pathway, our results suggest that TOR signaling regulates Pol I and Pol III transcription in response to nutrient growth signals.

* Corresponding author. Mailing address: Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2H7. Phone: (403) 492-9144. Fax: (403) 492-9556. E-mail: michael.schultz{at}ualberta.ca.

Mol Cell Biol, August 1998, p. 4463-4470, Vol. 18, No. 8
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Cipollina, C., van den Brink, J., Daran-Lapujade, P., Pronk, J. T., Vai, M., de Winde, J. H. (2008). Revisiting the role of yeast Sfp1 in ribosome biogenesis and cell size control: a chemostat study. Microbiology 154: 337-346 [Abstract] [Full Text]  
  • Grewal, S. S., Evans, J. R., Edgar, B. A. (2007). Drosophila TIF-IA is required for ribosome synthesis and cell growth and is regulated by the TOR pathway. JCB 179: 1105-1113 [Abstract] [Full Text]  
  • Zurita-Martinez, S. A., Puria, R., Pan, X., Boeke, J. D., Cardenas, M. E. (2007). Efficient Tor Signaling Requires a Functional Class C Vps Protein Complex in Saccharomyces cerevisiae. Genetics 176: 2139-2150 [Abstract] [Full Text]  
  • Weisman, R., Roitburg, I., Schonbrun, M., Harari, R., Kupiec, M. (2007). Opposite Effects of Tor1 and Tor2 on Nitrogen Starvation Responses in Fission Yeast. Genetics 175: 1153-1162 [Abstract] [Full Text]  
  • Alvarez, B., Moreno, S. (2006). Fission yeast Tor2 promotes cell growth and represses cell differentiation. J. Cell Sci. 119: 4475-4485 [Abstract] [Full Text]  
  • Michels, A. A., Hernandez, N. (2006). Does Pol I talk to Pol II? Coordination of RNA polymerases in ribosome biogenesis. Genes Dev. 20: 1982-1985 [Full Text]  
  • Laferte, A., Favry, E., Sentenac, A., Riva, M., Carles, C., Chedin, S. (2006). The transcriptional activity of RNA polymerase I is a key determinant for the level of all ribosome components. Genes Dev. 20: 2030-2040 [Abstract] [Full Text]  
  • Oakes, M. L., Siddiqi, I., French, S. L., Vu, L., Sato, M., Aris, J. P., Beyer, A. L., Nomura, M. (2006). Role of Histone Deacetylase Rpd3 in Regulating rRNA Gene Transcription and Nucleolar Structure in Yeast. Mol. Cell. Biol. 26: 3889-3901 [Abstract] [Full Text]  
  • Steinboeck, F., Krupanska, L., Bogusch, A., Kaufmann, A., Heidenreich, E. (2006). Novel Regulatory Properties of Saccharomyces cerevisiae Arp4.. J Biochem 139: 741-751 [Abstract] [Full Text]  
  • Swaminathan, S., Masek, T., Molin, C., Pospisek, M., Sunnerhagen, P. (2006). Rck2 Is Required for Reprogramming of Ribosomes during Oxidative Stress. Mol. Biol. Cell 17: 1472-1482 [Abstract] [Full Text]  
  • Martinet, W., De Meyer, G. R.Y., Andries, L., Herman, A. G., Kockx, M. M. (2006). In Situ Detection of Starvation-induced Autophagy. J. Histochem. Cytochem. 54: 85-96 [Abstract] [Full Text]  
  • Conesa, C., Ruotolo, R., Soularue, P., Simms, T. A., Donze, D., Sentenac, A., Dieci, G. (2005). Modulation of Yeast Genome Expression in Response to Defective RNA Polymerase III-Dependent Transcription. Mol. Cell. Biol. 25: 8631-8642 [Abstract] [Full Text]  
  • Mayer, C., Bierhoff, H., Grummt, I. (2005). The nucleolus as a stress sensor: JNK2 inactivates the transcription factor TIF-IA and down-regulates rRNA synthesis. Genes Dev. 19: 933-941 [Abstract] [Full Text]  
  • Imazawa, Y., Hisatake, K., Mitsuzawa, H., Matsumoto, M., Tsukui, T., Nakagawa, K., Nakadai, T., Shimada, M., Ishihama, A., Nogi, Y. (2005). The Fission Yeast Protein Ker1p Is an Ortholog of RNA Polymerase I Subunit A14 in Saccharomyces cerevisiae and Is Required for Stable Association of Rrn3p and RPA21 in RNA Polymerase I. J. Biol. Chem. 280: 11467-11474 [Abstract] [Full Text]  
  • Inoki, K., Ouyang, H., Li, Y., Guan, K.-L. (2005). Signaling by Target of Rapamycin Proteins in Cell Growth Control. Microbiol. Mol. Biol. Rev. 69: 79-100 [Abstract] [Full Text]  
  • Desai, N., Lee, J., Upadhya, R., Chu, Y., Moir, R. D., Willis, I. M. (2005). Two Steps in Maf1-dependent Repression of Transcription by RNA Polymerase III. J. Biol. Chem. 280: 6455-6462 [Abstract] [Full Text]  
  • Zurita-Martinez, S. A., Cardenas, M. E. (2005). Tor and Cyclic AMP-Protein Kinase A: Two Parallel Pathways Regulating Expression of Genes Required for Cell Growth. Eukaryot Cell 4: 63-71 [Abstract] [Full Text]  
  • Hossain, M. S, Kurokawa, K., Akimitsu, N., Sekimizu, K. (2004). DNA topoisomerase II is required for the G0-to-S phase transition in Drosophila Schneider cells, but not in yeast. GENES CELLS 9: 905-917 [Abstract] [Full Text]  
  • Kapahi, P., Zid, B. (2004). TOR Pathway: Linking Nutrient Sensing to Life Span. Sci Aging Knowl Environ 2004: pe34-pe34 [Abstract] [Full Text]  
  • Hay, N., Sonenberg, N. (2004). Upstream and downstream of mTOR. Genes Dev. 18: 1926-1945 [Abstract] [Full Text]  
  • James, M. J., Zomerdijk, J. C. B. M. (2004). Phosphatidylinositol 3-Kinase and mTOR Signaling Pathways Regulate RNA Polymerase I Transcription in Response to IGF-1 and Nutrients. J. Biol. Chem. 279: 8911-8918 [Abstract] [Full Text]  
  • Mayer, C., Zhao, J., Yuan, X., Grummt, I. (2004). mTOR-dependent activation of the transcription factor TIF-IA links rRNA synthesis to nutrient availability. Genes Dev. 18: 423-434 [Abstract] [Full Text]  
  • Claypool, J. A., French, S. L., Johzuka, K., Eliason, K., Vu, L., Dodd, J. A., Beyer, A. L., Nomura, M. (2004). Tor Pathway Regulates Rrn3p-dependent Recruitment of Yeast RNA Polymerase I to the Promoter but Does Not Participate in Alteration of the Number of Active Genes. Mol. Biol. Cell 15: 946-956 [Abstract] [Full Text]  
  • Drenan, R. M., Liu, X., Bertram, P. G., Zheng, X. F. S. (2004). FKBP12-Rapamycin-associated Protein or Mammalian Target of Rapamycin (FRAP/mTOR) Localization in the Endoplasmic Reticulum and the Golgi Apparatus. J. Biol. Chem. 279: 772-778 [Abstract] [Full Text]  
  • Schmelzle, T., Beck, T., Martin, D. E., Hall, M. N. (2004). Activation of the RAS/Cyclic AMP Pathway Suppresses a TOR Deficiency in Yeast. Mol. Cell. Biol. 24: 338-351 [Abstract] [Full Text]  
  • Jones, D. L., Petty, J., Hoyle, D. C., Hayes, A., Ragni, E., Popolo, L., Oliver, S. G., Stateva, L. I. (2003). Transcriptome profiling of a Saccharomyces cerevisiae mutant with a constitutively activated Ras/cAMP pathway. Physiol. Genomics 16: 107-118 [Abstract] [Full Text]  
  • Roberts, D. N., Stewart, A. J., Huff, J. T., Cairns, B. R. (2003). The RNA polymerase III transcriptome revealed by genome-wide localization and activity-occupancy relationships. Proc. Natl. Acad. Sci. USA 100: 14695-14700 [Abstract] [Full Text]  
  • Hannan, K. M., Brandenburger, Y., Jenkins, A., Sharkey, K., Cavanaugh, A., Rothblum, L., Moss, T., Poortinga, G., McArthur, G. A., Pearson, R. B., Hannan, R. D. (2003). mTOR-Dependent Regulation of Ribosomal Gene Transcription Requires S6K1 and Is Mediated by Phosphorylation of the Carboxy-Terminal Activation Domain of the Nucleolar Transcription Factor UBF{dagger}. Mol. Cell. Biol. 23: 8862-8877 [Abstract] [Full Text]  
  • Bro, C., Regenberg, B., Lagniel, G., Labarre, J., Montero-Lomeli, M., Nielsen, J. (2003). Transcriptional, Proteomic, and Metabolic Responses to Lithium in Galactose-grown Yeast Cells. J. Biol. Chem. 278: 32141-32149 [Abstract] [Full Text]  
  • Grummt, I. (2003). Life on a planet of its own: regulation of RNA polymerase I transcription in the nucleolus. Genes Dev. 17: 1691-1702 [Full Text]  
  • Alvarez, B., Garrido, E., Garcia-Sanz, J. A., Carrera, A. C. (2003). Phosphoinositide 3-Kinase Activation Regulates Cell Division Time by Coordinated Control of Cell Mass and Cell Cycle Progression Rate. J. Biol. Chem. 278: 26466-26473 [Abstract] [Full Text]  
  • Bonenfant, D., Schmelzle, T., Jacinto, E., Crespo, J. L., Mini, T., Hall, M. N., Jenoe, P. (2003). Quantitation of changes in protein phosphorylation: A simple method based on stable isotope labeling and mass spectrometry. Proc. Natl. Acad. Sci. USA 100: 880-885 [Abstract] [Full Text]  
  • Rohde, J. R., Cardenas, M. E. (2003). The Tor Pathway Regulates Gene Expression by Linking Nutrient Sensing to Histone Acetylation. Mol. Cell. Biol. 23: 629-635 [Abstract] [Full Text]  
  • Crespo, J. L., Hall, M. N. (2002). Elucidating TOR Signaling and Rapamycin Action: Lessons from Saccharomyces cerevisiae. Microbiol. Mol. Biol. Rev. 66: 579-591 [Abstract] [Full Text]  
  • Gelperin, D., Horton, L., DeChant, A., Hensold, J., Lemmon, S. K. (2002). Loss of Ypk1 Function Causes Rapamycin Sensitivity, Inhibition of Translation Initiation and Synthetic Lethality in 14-3-3-Deficient Yeast. Genetics 161: 1453-1464 [Abstract] [Full Text]  
  • Johnston, I. M., Allison, S. J., Morton, J. P., Schramm, L., Scott, P. H., White, R. J. (2002). CK2 Forms a Stable Complex with TFIIIB and Activates RNA Polymerase III Transcription in Human Cells. Mol. Cell. Biol. 22: 3757-3768 [Abstract] [Full Text]  
  • Crespo, J. L., Powers, T., Fowler, B., Hall, M. N. (2002). The TOR-controlled transcription activators GLN3, RTG1, and RTG3 are regulated in response to intracellular levels of glutamine. Proc. Natl. Acad. Sci. USA 99: 6784-6789 [Abstract] [Full Text]  
  • Cutler, N. S., Pan, X., Heitman, J., Cardenas, M. E. (2001). The TOR Signal Transduction Cascade Controls Cellular Differentiation in Response to Nutrients. Mol. Biol. Cell 12: 4103-4113 [Abstract] [Full Text]  
  • Cruz, M. C., Goldstein, A. L., Blankenship, J., Del Poeta, M., Perfect, J. R., McCusker, J. H., Bennani, Y. L., Cardenas, M. E., Heitman, J. (2001). Rapamycin and Less Immunosuppressive Analogs Are Toxic to Candida albicans and Cryptococcus neoformans via FKBP12-Dependent Inhibition of TOR. Antimicrob. Agents Chemother. 45: 3162-3170 [Abstract] [Full Text]  
  • Abeliovich, H., Klionsky, D. J. (2001). Autophagy in Yeast: Mechanistic Insights and Physiological Function. Microbiol. Mol. Biol. Rev. 65: 463-479 [Abstract] [Full Text]  
  • Raught, B., Gingras, A.-C., Sonenberg, N. (2001). The target of rapamycin (TOR) proteins. Proc. Natl. Acad. Sci. USA 98: 7037-7044 [Abstract] [Full Text]  
  • Kuruvilla, F. G., Shamji, A. F., Schreiber, S. L. (2001). Carbon- and nitrogen-quality signaling to translation are mediated by distinct GATA-type transcription factors. Proc. Natl. Acad. Sci. USA 98: 7283-7288 [Abstract] [Full Text]  
  • Liu, J., D. Prickett, T., Elliott, E., Meroni, G., Brautigan, D. L. (2001). Phosphorylation and microtubule association of the Opitz syndrome protein mid-1 is regulated by protein phosphatase 2A via binding to the regulatory subunit alpha 4. Proc. Natl. Acad. Sci. USA 10.1073/pnas.111154698v1 [Abstract] [Full Text]  
  • Liang, X. H., Yu, J., Brown, K., Levine, B. (2001). Beclin 1 Contains a Leucine-rich Nuclear Export Signal That Is Required for Its Autophagy and Tumor Suppressor Function. Cancer Res. 61: 3443-3449 [Abstract] [Full Text]  
  • WARNER, J.R., VILARDELL, J., SOHN, J.H. (2001). Economics of Ribosome Biosynthesis. Cold Spring Harb Symp Quant Biol 66: 567-574 [Abstract]  
  • Abeliovich, H., Dunn, W. A. , Jr., Kim, J., Klionsky, D. J. (2000). Dissection of Autophagosome Biogenesis into Distinct Nucleation and Expansion Steps. JCB 151: 1025-1034 [Abstract] [Full Text]  
  • Komeili, A., Wedaman, K. P., O'Shea, E. K., Powers, T. (2000). Mechanism of Metabolic Control: Target of Rapamycin Signaling Links Nitrogen Quality to the Activity of the Rtg1 and Rtg3 Transcription Factors. JCB 151: 863-878 [Abstract] [Full Text]  
  • Chan, T.-F., Carvalho, J., Riles, L., Zheng, X. F. S. (2000). A chemical genomics approach toward understanding the global functions of the target of rapamycin protein (TOR). Proc. Natl. Acad. Sci. USA 10.1073/pnas.240444197v1 [Abstract] [Full Text]  
  • Abe, F., Horikoshi, K. (2000). Tryptophan Permease Gene TAT2 Confers High-Pressure Growth in Saccharomyces cerevisiae. Mol. Cell. Biol. 20: 8093-8102 [Abstract] [Full Text]  
  • Zhang, H., Stallock, J. P., Ng, J. C., Reinhard, C., Neufeld, T. P. (2000). Regulation of cellular growth by the Drosophila target of rapamycin dTOR. Genes Dev. 14: 2712-2724 [Abstract] [Full Text]  
  • Cosentino, G. P., Schmelzle, T., Haghighat, A., Helliwell, S. B., Hall, M. N., Sonenberg, N. (2000). Eap1p, a Novel Eukaryotic Translation Initiation Factor 4E-Associated Protein in Saccharomyces cerevisiae. Mol. Cell. Biol. 20: 4604-4613 [Abstract] [Full Text]  
  • Hardwick, J. S., Kuruvilla, F. G., Tong, J. K., Shamji, A. F., Schreiber, S. L. (1999). Rapamycin-modulated transcription defines the subset of nutrient-sensitive signaling pathways directly controlled by the Tor proteins. Proc. Natl. Acad. Sci. USA 96: 14866-14870 [Abstract] [Full Text]  
  • Cardenas, M. E., Cutler, N. S., Lorenz, M. C., Di Como, C. J., Heitman, J. (1999). The TOR signaling cascade regulates gene expression in response to nutrients. Genes Dev. 13: 3271-3279 [Abstract] [Full Text]  
  • Louro, I. D., McKie-Bell, P., Gosnell, H., Brindley, B. C., Bucy, R. P., Ruppert, J. M. (1999). The Zinc Finger Protein GLI Induces Cellular Sensitivity to the mTOR Inhibitor Rapamycin. Cell Growth Differ. 10: 503-516 [Abstract] [Full Text]  
  • Powers, T., Walter, P. (1999). Regulation of Ribosome Biogenesis by the Rapamycin-sensitive TOR-signaling Pathway in Saccharomyces cerevisiae. Mol. Biol. Cell 10: 987-1000 [Abstract] [Full Text]  
  • Bertram, P. G., Choi, J. H., Carvalho, J., Ai, W., Zeng, C., Chan, T.-F., Zheng, X. F. S. (2000). Tripartite Regulation of Gln3p by TOR, Ure2p, and Phosphatases. J. Biol. Chem. 275: 35727-35733 [Abstract] [Full Text]  
  • Scott, P. H., Cairns, C. A., Sutcliffe, J. E., Alzuherri, H. M., McLees, A., Winter, A. G., White, R. J. (2001). Regulation of RNA Polymerase III Transcription during Cell Cycle Entry. J. Biol. Chem. 276: 1005-1014 [Abstract] [Full Text]  
  • Weisman, R., Choder, M. (2001). The Fission Yeast TOR Homolog, tor1+, Is Required for the Response to Starvation and Other Stresses via a Conserved Serine. J. Biol. Chem. 276: 7027-7032 [Abstract] [Full Text]  
  • Crespo, J. L., Daicho, K., Ushimaru, T., Hall, M. N. (2001). The GATA Transcription Factors GLN3 and GAT1 Link TOR to Salt Stress in Saccharomyces cerevisiae. J. Biol. Chem. 276: 34441-34444 [Abstract] [Full Text]  
  • Rohde, J., Heitman, J., Cardenas, M. E. (2001). The TOR Kinases Link Nutrient Sensing to Cell Growth. J. Biol. Chem. 276: 9583-9586 [Abstract] [Full Text]  
  • Liu, J., Prickett, T. D., Elliott, E., Meroni, G., Brautigan, D. L. (2001). Phosphorylation and microtubule association of the Opitz syndrome protein mid-1 is regulated by protein phosphatase 2A via binding to the regulatory subunit alpha 4. Proc. Natl. Acad. Sci. USA 98: 6650-6655 [Abstract] [Full Text]  
  • Chan, T.-F., Carvalho, J., Riles, L., Zheng, X. F. S. (2000). A chemical genomics approach toward understanding the global functions of the target of rapamycin protein (TOR). Proc. Natl. Acad. Sci. USA 97: 13227-13232 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»