Browse > Article
http://dx.doi.org/10.5808/GI.2010.8.4.177

Genomewide Profiling of Rapamycin Sensitivity in Saccharomyces cerevisiae on Synthetic Medium  

Chang, Yeon-Ji (School of Biological Sciences, and Research Center for Functional Cellulomics, Institute of Microbiology, Seoul National University)
Shin, Chun-Shik (School of Biological Sciences, and Research Center for Functional Cellulomics, Institute of Microbiology, Seoul National University)
Han, Dong-Hun (Korea Science Academy)
Kim, Ji-Yun (Korea Science Academy)
Kim, Kang-In (Korea Science Academy)
Kwon, Yong-Min (Korea Science Academy)
Huh, Won-Ki (School of Biological Sciences, and Research Center for Functional Cellulomics, Institute of Microbiology, Seoul National University)
Abstract
The target of rapamycin (TOR) signaling pathway is a conserved pathway that regulates eukaryotic cell growth in response to environmental cues. Chemical genomic approaches that profile rapamycin sensitivity of yeast deletion strains have given insights into the function of TOR signaling pathway. In the present study, we analyzed the rapamycin sensitivity of yeast deletion library strains on synthetic medium. As a result, we identified 130 strains that are hypersensitive or resistant to rapamycin compared with wild-type cells. Among them, 36 genes are newly identified to be related to rapamycin sensitivity. Moreover, we found 16 strains that show alteration in rapamycin sensitivity between complex and synthetic media. We suggest that these genes may be involved in part of TOR signaling activities that is differentially regulated by media composition.
Keywords
rapamycin; Saccharomyces cerevisiae; TOR signaling pathway; yeast deletion library;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Wu, J., Tolstykh, T., Lee, J., Boyd, K., Stock, J.B., and Broach, J.R. (2000). Carboxyl methylation of the phosphoprotein phosphatase 2A catalytic subunit promotes its functional association with regulatory subunits in vivo. EMBO J. 19, 5672-5681.   DOI
2 Xie, M.W., Jin, F., Hwang, H., Hwang, S., Anand, V., Duncan, M.C., and Huang, J. (2005). Insights into TOR function and rapamycin response: chemical genomic profiling by using a high-density cell array method. Proc. Natl. Acad. Sci. USA 102, 7215-7220.   DOI
3 Rohde, J., Heitman, J., and Cardenas, M.E. (2001). The TOR kinases link nutrient sensing to cell growth. J. Biol. Chem. 276, 9583-9586.   DOI
4 Rohde, J.R., Campbell, S., Zurita-Martinez, S.A., Cutler, N.S., Ashe, M., and Cardenas, M.E. (2004). TOR controls transcriptional and translational programs via Sap-Sit4 protein phosphatase signaling effectors. Mol. Cell Biol. 24, 8332-8341.   DOI
5 Sherman, F. (2002). Getting started with yeast. Methods Enzymol 350, 3-41.   DOI
6 Snowdon, C., Hlynialuk, C., and van der Merwe, G. (2008). Components of the Vid30c are needed for the rapamycin-induced degradation of the high-affinity hexose transporter Hxt7p in Saccharomyces cerevisiae. FEMS Yeast Res. 8, 204-216.   DOI
7 Takeda, M., Chen, W.J., Saltzgaber, J., and Douglas, M.G. (1986). Nuclear genes encoding the yeast mitochondrial ATPase complex. Analysis of ATP1 coding the F1-ATPase alpha-subunit and its assembly. J. Biol. Chem. 261, 15126-15133.
8 von Mering, C., Huynen, M., Jaeggi, D., Schmidt, S., Bork, P., and Snel, B. (2003). STRING: a database of predicted functional associations between proteins. Nucl. Acids Res. 31, 258-261.   DOI   ScienceOn
9 Weinberger, M., Mesquita, A., Caroll, T., Marks, L., Yang, H., Zhang, Z., Ludovico, P., and Burhans, W.C. (2010). Growth signaling promotes chronological aging in budding yeast by inducing superoxide anions that inhibit quiescence. Aging (Albany NY) 2, 709-726.   DOI
10 Winzeler, E.A., Shoemaker, D.D., Astromoff, A., Liang, H., Anderson, K., Andre, B., Bangham, R., Benito, R., Boeke, J.D., Bussey, H., Chu, A.M., Connelly, C., Davis, K., Dietrich, F., Dow, S.W., El Bakkoury, M., Foury, F., Friend, S.H., Gentalen, E., Giaever, G., Hegemann, J.H., Jones, T., Laub, M., Liao, H., Liebundguth, N., Lockhart, D.J., Lucau-Danila, A., Lussier, M., M'Rabet, N., Menard, P., Mittmann, M., Pai, C., Rebischung, C., Revuelta, J.L., Riles, L., Roberts, C.J., Ross-MacDonald, P., Scherens, B., Snyder, M., Sookhai-Mahadeo, S., Storms, R.K., Veronneau, S., Voet, M., Volckaert, G., Ward, T.R., Wysocki, R., Yen, G.S., Yu, K., Zimmermann, K., Philippsen, P., Johnston, M., and Davis, R.W. (1999). Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. Science 285, 901-906.   DOI
11 Koltin, Y., Faucette, L., Bergsma, D.J., Levy, M.A., Cafferkey, R., Koser, P.L., Johnson, R.K., and Livi, G.P. (1991). Rapamycin sensitivity in Saccharomyces cerevisiae is mediated by a peptidyl-prolyl cis-trans isomerase related to human FK506-binding protein. Mol. Cell Biol. 11, 1718-1723.   DOI
12 Kaeberlein, M., Powers, R.W., 3rd, Steffen, K.K., Westman, E.A., Hu, D., Dang, N., Kerr, E.O., Kirkland, K.T., Fields, S., and Kennedy, B.K. (2005). Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science 310, 1193-1196.   DOI
13 Kamada, Y., Sekito, T., and Ohsumi, Y. (2004). Autophagy in yeast: a TOR-mediated response to nutrient starvation. Curr. Top Microbiol. Immunol. 279, 73-84.   DOI
14 Kim, D.H., Sarbassov, D.D., Ali, S.M., King, J.E., Latek, R.R., Erdjument-Bromage, H., Tempst, P., and Sabatini, D.M. (2002). mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell 110, 163-175.   DOI
15 Lastauskiene, E., and Citavicius, D. (2008). Influence of RAS genes on yeast Saccharomyces cerevisiae cell viability in acid environment. Biologija 54, 150-155.   DOI
16 Leidel, S., Pedrioli, P.G., Bucher, T., Brost, R., Costanzo, M., Schmidt, A., Aebersold, R., Boone, C., Hofmann, K., and Peter, M. (2009). Ubiquitin-related modifier Urm1 acts as a sulphur carrier in thiolation of eukaryotic transfer RNA. Nature 458, 228-232.   DOI
17 Liu, Z., and Butow, R.A. (2006). Mitochondrial retrograde signaling. Annu. Rev. Genet. 40, 159-185.   DOI
18 Loewith, R., Jacinto, E., Wullschleger, S., Lorberg, A., Crespo, J.L., Bonenfant, D., Oppliger, W., Jenoe, P., and Hall, M.N. (2002). Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol. Cell 10, 457-468.   DOI
19 Parsons, A.B., Brost, R.L., Ding, H., Li, Z., Zhang, C., Sheikh, B., Brown, G.W., Kane, P.M., Hughes, T.R., and Boone, C. (2004). Integration of chemical-genetic and genetic interaction data links bioactive compounds to cellular target pathways. Nat. Biotechnol. 22, 62-69.   DOI
20 Mayer, C., and Grummt, I. (2006). Ribosome biogenesis and cell growth: mTOR coordinates transcription by all three classes of nuclear RNA polymerases. Oncogene 25, 6384-6391.   DOI
21 Giaever, G., Chu, A.M., Ni, L., Connelly, C., Riles, L., Veronneau, S., Dow, S., Lucau-Danila, A., Anderson, K., Andre, B., Arkin, A.P., Astromoff, A., El-Bakkoury, M., Bangham, R., Benito, R., Brachat, S., Campanaro, S., Curtiss, M., Davis, K., Deutschbauer, A., Entian, K.D., Flaherty, P., Foury, F., Garfinkel, D.J., Gerstein, M., Gotte, D., Guldener, U., Hegemann, J.H., Hempel, S., Herman, Z., Jaramillo, D.F., Kelly, D.E., Kelly, S.L., Kotter, P., LaBonte, D., Lamb, D.C., Lan, N., Liang, H., Liao, H., Liu, L., Luo, C., Lussier, M., Mao, R., Menard, P., Ooi, S.L., Revuelta, J.L., Roberts, C.J., Rose, M., Ross-Macdonald, P., Scherens, B., Schimmack, G., Shafer, B., Shoemaker, D.D., Sookhai-Mahadeo, S., Storms, R.K., Strathern, J.N., Valle, G., Voet, M., Volckaert, G., Wang, C.Y., Ward, T.R., Wilhelmy, J., Winzeler, E.A., Yang, Y., Yen, G., Youngman, E., Yu, K., Bussey, H., Boeke, J.D., Snyder, M., Philippsen, P., Davis, R.W., and Johnston, M. (2002). Functional profiling of the Saccharomyces cerevisiae genome. Nature 418, 387-391.   DOI
22 Hara, K., Maruki, Y., Long, X., Yoshino, K., Oshiro, N., Hidayat, S., Tokunaga, C., Avruch, J., and Yonezawa, K. (2002). Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell 110, 177-189.   DOI
23 Heitman, J., Movva, N.R., Hiestand, P.C., and Hall, M.N. (1991). FK 506-binding protein proline rotamase is a target for the immunosuppressive agent FK 506 in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 88, 1948-1952.   DOI
24 Huber, A., Bodenmiller, B., Uotila, A., Stahl, M., Wanka, S., Gerrits, B., Aebersold, R., and Loewith, R. (2009). Characterization of the rapamycin-sensitive phosphoproteome reveals that Sch9 is a central coordinator of protein synthesis. Genes Dev. 23, 1929-1943.   DOI
25 Abe, F., and Minegishi, H. (2008). Global screening of genes essential for growth in high-pressure and cold environments: searching for basic adaptive strategies using a yeast deletion library. Genetics 178, 851-872.   DOI
26 Huh, W.K., Falvo, J.V., Gerke, L.C., Carroll, A.S., Howson, R.W., Weissman, J.S., and O'Shea, E.K. (2003). Global analysis of protein localization in budding yeast. Nature 425, 686-691.   DOI
27 Jensen, L.J., Kuhn, M., Stark, M., Chaffron, S., Creevey, C., Muller, J., Doerks, T., Julien, P., Roth, A., Simonovic, M., Bork, P., and von Mering, C. (2009). STRING 8--a global view on proteins and their functional interactions in 630 organisms. Nucl. Acids Res. 37, D412-416.   DOI
28 Kaeberlein, M., and Guarente, L. (2002). Saccharomyces cerevisiae MPT5 and SSD1 function in parallel pathways to promote cell wall integrity. Genetics 160, 83-95.
29 Beck, T., and Hall, M.N. (1999). The TOR signalling pathway controls nuclear localization of nutrient-regulated transcription factors. Nature 402, 689-692.   DOI
30 Carvalho, J., and Zheng, X.F. (2003). Domains of Gln3p interacting with karyopherins, Ure2p, and the target of rapamycin protein. J. Biol. Chem. 278, 16878-16886.   DOI
31 Chan, T.F., Carvalho, J., Riles, L., and Zheng, X.F. (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.   DOI
32 Fournier, M.L., Paulson, A., Pavelka, N., Mosley, A.L., Gaudenz, K., Bradford, W.D., Glynn, E., Li, H., Sardiu, M.E., Fleharty, B., Seidel, C., Florens, L., and Washburn, M.P. (2010). Delayed correlation of mRNA and protein expression in rapamycin-treated cells and a role for Ggc1 in cellular sensitivity to rapamycin. Mol. Cell Proteomics 9, 271-284.   DOI
33 Di Como, C.J., and Arndt, K.T. (1996). Nutrients, via the Tor proteins, stimulate the association of Tap42 with type 2A phosphatases. Genes Dev. 10, 1904-1916.   DOI
34 Dudley, A.M., Janse, D.M., Tanay, A., Shamir, R., and Church, G.M. (2005). A global view of pleiotropy and phenotypically derived gene function in yeast. Mol. Syst. Biol. 1, 2005.0001.