Skip to main content
SpringerLink
Log in

Contributions of Saccharomyces cerevisiae to Understanding Mammalian Gene Function and Therapy

  • Protocol
  • First Online:
Yeast Systems Biology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 759))

Abstract

Due to its genetic tractability and ease of manipulation, the yeast Saccharomyces cerevisiae has been extensively used as a model organism to understand how eukaryotic cells grow, divide, and respond to environmental changes. In this chapter, we reasoned that functional annotation of novel genes revealed by sequencing should adopt an integrative approach including both bioinformatics and experimental analysis to reveal functional conservation and divergence of complexes and pathways. The techniques and resources generated for systems biology studies in yeast have found a wide range of applications. Here we focused on using these technologies in revealing functions of genes from mammals, in identifying targets of novel and known drugs and in screening drugs targeting specific proteins and/or protein–protein interactions.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Dolinski, K., and Botstein, D. (2007) Orthology and functional conservation in eukaryotes. Annu. Rev. Genet. 41, 465–507.

    PubMed  CAS  Google Scholar 

  2. Kataoka, T., Powers, S., Cameron, S., et al. (1985) Functional homology of mammalian and yeast RAS genes. Cell 40, 19–26.

    PubMed  CAS  Google Scholar 

  3. Lee, M. G., and Nurse, P. (1987) Complementation used to clone a human homologue of the fission yeast cell cycle control gene cdc2. Nature 327, 31–35.

    PubMed  CAS  Google Scholar 

  4. Goffeau, A., Barrell, B. G., Bussey, H., et al. (1996) Life with 6000 genes. Science 274, 546, 563–567.

    Google Scholar 

  5. Suter, B., Auerbach, D., and Stagljar, I. (2006) Yeast-based functional genomics and proteomics technologies: the first 15 years and beyond. Biotechniques 40, 625–644.

    PubMed  CAS  Google Scholar 

  6. Winzeler, E. A., Shoemaker, D. D., Astromoff, A., et al. (1999) Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. Science 285, 901–906.

    PubMed  CAS  Google Scholar 

  7. Hillenmeyer, M. E., Fung, E., Wildenhain, J., et al. (2008) The chemical genomic portrait of yeast: uncovering a phenotype for all genes. Science 320, 362–365.

    PubMed  CAS  Google Scholar 

  8. Giaever, G., Chu, A. M., Ni, L., et al. (2002) Functional profiling of the Saccharomyces cerevisiae genome. Nature 418, 387–391.

    PubMed  CAS  Google Scholar 

  9. Deutschbauer, A. M., Jaramillo, D. F., Proctor, M., et al. (2005) Mechanisms of haploinsufficiency revealed by genome-wide profiling in yeast. Genetics 169, 1915–1925.

    PubMed  CAS  Google Scholar 

  10. Mager, W. H., and Winderickx, J. (2005) Yeast as a model for medical and medicinal research. Trends Pharmacol. Sci. 26, 265–273.

    PubMed  CAS  Google Scholar 

  11. Oliver, S. G. (2006) From genomes to systems: the path with yeast. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 361, 477–482.

    PubMed  CAS  Google Scholar 

  12. Liolios, K., Tavernarakis, N., Hugenholtz, P., and Kyrpides, N. C. (2006) The genomes on line database (GOLD) v.2: a monitor of genome projects worldwide. Nucleic Acids Res. 34, D332–D334.

    PubMed  CAS  Google Scholar 

  13. Lee, D., Redfern, O., and Orengo, C. (2007) Predicting protein function from sequence and structure. Nat. Rev. Mol. Cell Biol. 8, 995–1005.

    PubMed  CAS  Google Scholar 

  14. Velours, J., Vaillier, J., Paumard, P., Soubannier, V., Lai-Zhang, J., and Mueller, D. M. (2001) Bovine coupling factor 6, with just 14.5% shared identity, replaces subunit h in the yeast ATP synthase. J. Biol. Chem. 276, 8602–8607.

    PubMed  CAS  Google Scholar 

  15. Dann, S. G., Selvaraj, A., and Thomas, G. (2007) mTOR Complex1-S6K1 signaling: at the crossroads of obesity, diabetes and cancer. Trends Mol. Med. 13, 252–259.

    PubMed  CAS  Google Scholar 

  16. Sobko, A. (2006) Systems biology of AGC kinases in fungi. Sci. STKE 2006, re9.

    PubMed  Google Scholar 

  17. Urban, J., Soulard, A., Huber, A., et al. (2007) Sch9 is a major target of TORC1 in Saccharomyces cerevisiae. Mol. Cell 26, 663–674.

    PubMed  CAS  Google Scholar 

  18. Oliver, S. G., van der Aart, Q. J., Agostoni-Carbone, M. L., et al. (1992) The complete DNA sequence of yeast chromosome III. Nature 357, 38–46.

    PubMed  CAS  Google Scholar 

  19. Ouzounis, C., and Sander, C. (1993) Homology of the NifS family of proteins to a new class of pyridoxal phosphate-dependent enzymes. FEBS Lett. 322, 159–164.

    PubMed  CAS  Google Scholar 

  20. Gross, S., and Moore, C. (2001) Five subunits are required for reconstitution of the cleavage and polyadenylation activities of Saccharomyces cerevisiae cleavage factor I. Proc. Natl. Acad. Sci. USA 98, 6080–6085.

    PubMed  CAS  Google Scholar 

  21. Ramirez, A., Shuman, S., and Schwer, B. (2008) Human RNA 5'-kinase (hClp1) can function as a tRNA splicing enzyme in vivo. RNA 14, 1737–1745.

    PubMed  CAS  Google Scholar 

  22. Hartwell, L. H. (2004) Yeast and cancer. Biosci. Rep. 24, 523–544.

    PubMed  Google Scholar 

  23. Grunewald, S., Matthijs, G., and Jaeken, J. (2002) Congenital disorders of glycosylation: a review. Pediatr. Res. 52, 618–624.

    PubMed  Google Scholar 

  24. Zeviani, M., and Carelli, V. (2007) Mitochondrial disorders. Curr. Opin. Neurol. 20, 564–571.

    PubMed  CAS  Google Scholar 

  25. Botstein, D., Chervitz, S. A., and Cherry, J. M. (1997) Yeast as a model organism. Science 277, 1259–1260.

    PubMed  CAS  Google Scholar 

  26. Ooi, S. L., Pan, X., Peyser, B. D., et al. (2006) Global synthetic-lethality analysis and yeast functional profiling. Trends Genet. 22, 56–63.

    PubMed  CAS  Google Scholar 

  27. Zhang, N., Osborn, M., Gitsham, P., Yen, K., Miller, J. R., and Oliver, S. G. (2003) Using yeast to place human genes in functional categories. Gene 303, 121–129.

    PubMed  CAS  Google Scholar 

  28. Wishart, J. A., Hayes, A., Wardleworth, L., Zhang, N., and Oliver, S. G. (2005) Doxycycline, the drug used to control the tet-regulatable promoter system, has no effect on global gene expression in Saccharomyces cerevisiae. Yeast 22, 565–569.

    PubMed  CAS  Google Scholar 

  29. Mnaimneh, S., Davierwala, A. P., Haynes, J., et al. (2004) Exploration of essential gene functions via titratable promoter alleles. Cell 118, 31–44.

    PubMed  CAS  Google Scholar 

  30. Kanemaki, M., Sanchez-Diaz, A., Gambus, A., and Labib, K. (2003) Functional proteomic identification of DNA replication proteins by induced proteolysis in vivo. Nature 423, 720–724.

    PubMed  CAS  Google Scholar 

  31. Sanchez-Diaz, A., Kanemaki, M., Marchesi, V., and Labib, K. (2004) Rapid depletion of budding yeast proteins by fusion to a heat-inducible degron. Sci. STKE 2004, PL8.

    Google Scholar 

  32. Terziyska, N., Grumbt, B., Kozany, C., and Hell, K. (2009) Structural and functional roles of the conserved cysteine residues of the redox-regulated import receptor Mia40 in the intermembrane space of mitochondria. J. Biol. Chem. 284, 1353–1363.

    PubMed  CAS  Google Scholar 

  33. Han, G. S., Sreenivas, A., Choi, M. G., et al. (2005) Expression of Human CTP synthetase in Saccharomyces cerevisiae reveals phosphorylation by protein kinase A. J. Biol. Chem. 280, 38328–38336.

    PubMed  CAS  Google Scholar 

  34. Sharma, S., Sommers, J. A., and Brosh, R. M., Jr. (2004) In vivo function of the conserved non-catalytic domain of Werner syndrome helicase in DNA replication. Hum. Mol. Genet. 13, 2247–2261.

    PubMed  CAS  Google Scholar 

  35. Aller, S. G., Eng, E. T., De Feo, C. J., and Unger, V. M. (2004) Eukaryotic CTR copper uptake transporters require two faces of the third transmembrane domain for helix packing, oligomerization, and function. J. Biol. Chem. 279, 53435–53441.

    PubMed  CAS  Google Scholar 

  36. Grillari, J., Ajuh, P., Stadler, G., et al. (2005) SNEV is an evolutionarily conserved splicing factor whose oligomerization is necessary for spliceosome assembly. Nucleic Acids Res. 33, 6868–6883.

    PubMed  CAS  Google Scholar 

  37. Boocock, G. R., Marit, M. R., and Rommens, J. M. (2006) Phylogeny, sequence conservation, and functional complementation of the SBDS protein family. Genomics 87, 758–771.

    PubMed  CAS  Google Scholar 

  38. Chang, C. P., Lin, G., Chen, S. J., Chiu, W. C., Chen, W. H., and Wang, C. C. (2008) Promoting the formation of an active synthetase/tRNA complex by a nonspecific tRNA-binding domain. J. Biol. Chem. 283, 30699–30706.

    PubMed  CAS  Google Scholar 

  39. Vaz, F. M., Houtkooper, R. H., Valianpour, F., Barth, P. G., and Wanders, R. J. (2003) Only one splice variant of the human TAZ gene encodes a functional protein with a role in cardiolipin metabolism. J. Biol. Chem. 278, 43089–43094.

    PubMed  CAS  Google Scholar 

  40. Ma, L., Vaz, F. M., Gu, Z., Wanders, R. J., and Greenberg, M. L. (2004) The human TAZ gene complements mitochondrial dysfunction in the yeast taz1Delta mutant. Implications for Barth syndrome. J. Biol. Chem. 279, 44394–44399.

    PubMed  CAS  Google Scholar 

  41. Tabuchi, M., Tanaka, N., Nishida-Kitayama, J., Ohno, H., and Kishi, F. (2002) Alternative splicing regulates the subcellular localization of divalent metal transporter 1 isoforms. Mol. Biol. Cell 13, 4371–4387.

    PubMed  CAS  Google Scholar 

  42. De Marcos Lousa, C., Trezeguet, V., Dianoux, A. C., Brandolin, G., and Lauquin, G. J. (2002) The human mitochondrial ADP/ATP carriers: kinetic properties and biogenesis of wild-type and mutant proteins in the yeast S. cerevisiae. Biochemistry 41, 14412–14420.

    PubMed  Google Scholar 

  43. Zhang, Y., and Spremulli, L. L. (1998) Identification and cloning of human mitochondrial translational release factor 1 and the ribosome recycling factor. Biochim. Biophys. Acta 1443, 245–250.

    PubMed  CAS  Google Scholar 

  44. Soleimanpour-Lichaei, H. R., Kuhl, I., Gaisne, M., et al. (2007) mtRF1a is a human mitochondrial translation release factor decoding the major termination codons UAA and UAG. Mol. Cell 27, 745–757.

    PubMed  CAS  Google Scholar 

  45. Tamburini, B. A., Carson, J. J., Adkins, M. W., and Tyler, J. K. (2005) Functional conservation and specialization among eukaryotic anti-silencing function 1 histone chaperones. Eukaryot. Cell 4, 1583–1590.

    PubMed  CAS  Google Scholar 

  46. Chiron, S., Suleau, A., and Bonnefoy, N. (2005) Mitochondrial translation: elongation factor tu is essential in fission yeast and depends on an exchange factor conserved in humans but not in budding yeast. Genetics 169, 1891–1901.

    PubMed  CAS  Google Scholar 

  47. St-Pierre, B., Liu, X., Kha, L. C., et al. (2005) Conserved and specific functions of mammalian ssu72. Nucleic Acids Res. 33, 464–477.

    PubMed  CAS  Google Scholar 

  48. Gao, X. D., Tachikawa, H., Sato, T., Jigami, Y., and Dean, N. (2005) Alg14 recruits Alg13 to the cytoplasmic face of the endoplasmic reticulum to form a novel bipartite UDP-N-acetylglucosamine transferase required for the second step of N-linked glycosylation. J. Biol. Chem. 280, 36254–36262.

    PubMed  CAS  Google Scholar 

  49. Ozanick, S., Krecic, A., Andersland, J., and Anderson, J. T. (2005) The bipartite structure of the tRNA m1A58 methyltransferase from S. cerevisiae is conserved in humans. RNA 11, 1281–1290.

    PubMed  CAS  Google Scholar 

  50. Otto, H., Conz, C., Maier, P., et al. (2005) The chaperones MPP11 and Hsp70L1 form the mammalian ribosome-associated complex. Proc. Natl. Acad. Sci. USA 102, 10064–10069.

    PubMed  CAS  Google Scholar 

  51. Proshkina, G. M., Shematorova, E. K., Proshkin, S. A., Zaros, C., Thuriaux, P., and Shpakovski, G. V. (2006) Ancient origin, functional conservation and fast evolution of DNA-dependent RNA polymerase III. Nucleic Acids Res. 34, 3615–3624.

    PubMed  CAS  Google Scholar 

  52. Loewith, R., Jacinto, E., Wullschleger, S., et al. (2002) Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol. Cell 10, 457–468.

    PubMed  CAS  Google Scholar 

  53. Wullschleger, S., Loewith, R., and Hall, M. N. (2006) TOR signaling in growth and metabolism. Cell 124, 471–484.

    PubMed  CAS  Google Scholar 

  54. De Virgilio, C., and Loewith, R. (2006) Cell growth control: little eukaryotes make big contributions. Oncogene 25, 6392–6415.

    PubMed  Google Scholar 

  55. Kim, E., Goraksha-Hicks, P., Li, L., Neufeld, T. P., and Guan, K. L. (2008) Regulation of TORC1 by Rag GTPases in nutrient response. Nat. Cell Biol. 10, 935–945.

    PubMed  CAS  Google Scholar 

  56. Berger, A. C., Vanderford, T. H., Gernert, K. M., Nichols, J. W., Faundez, V., and Corbett, A. H. (2005) Saccharomyces cerevisiae Npc2p is a functionally conserved homologue of the human Niemann-Pick disease type C 2 protein, hNPC2. Eukaryot. Cell 4, 1851–1862.

    PubMed  CAS  Google Scholar 

  57. Binda, M., Peli-Gulli, M. P., Bonfils, G., et al. (2009) The Vam6 GEF controls TORC1 by activating the EGO complex. Mol. Cell 35, 563–573.

    PubMed  CAS  Google Scholar 

  58. Sancak, Y., Peterson, T. R., Shaul, Y. D., et al. (2008) The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science 320, 1496–1501.

    PubMed  CAS  Google Scholar 

  59. Wieland, G., Orthaus, S., Ohndorf, S., Diekmann, S., and Hemmerich, P. (2004) Functional complementation of human centromere protein A (CENP-A) by Cse4p from Saccharomyces cerevisiae. Mol. Cell Biol. 24, 6620–6630.

    PubMed  CAS  Google Scholar 

  60. Ricardo, S., and Lehmann, R. (2009) An ABC transporter controls export of a Drosophila germ cell attractant. Science 323, 943–946.

    PubMed  CAS  Google Scholar 

  61. Wells, J. A., and McClendon, C. L. (2007) Reaching for high-hanging fruit in drug discovery at protein-protein interfaces. Nature 450, 1001–1009.

    PubMed  CAS  Google Scholar 

  62. Fields, S., and Song, O. (1989) A novel genetic system to detect protein-protein interactions. Nature 340, 245–246.

    PubMed  CAS  Google Scholar 

  63. Fromont-Racine, M., Rain, J. C., and Legrain, P. (1997) Toward a functional analysis of the yeast genome through exhaustive two-hybrid screens. Nat. Genet. 16, 277–282.

    PubMed  CAS  Google Scholar 

  64. Walhout, A. J., Temple, G. F., Brasch, M. A., et al. (2000) GATEWAY recombinational cloning: application to the cloning of large numbers of open reading frames or ORFeomes. Methods Enzymol. 328, 575–592.

    PubMed  CAS  Google Scholar 

  65. Uetz, P., Giot, L., Cagney, G., et al. (2000) A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae. Nature 403, 623–627.

    PubMed  CAS  Google Scholar 

  66. Ito, T., Chiba, T., Ozawa, R., Yoshida, M., Hattori, M., and Sakaki, Y. (2001) A comprehensive two-hybrid analysis to explore the yeast protein interactome. Proc. Natl. Acad. Sci. USA 98, 4569–4574.

    PubMed  CAS  Google Scholar 

  67. Mackay, J. P., Sunde, M., Lowry, J. A., Crossley, M., and Matthews, J. M. (2007) Protein interactions: is seeing believing? Trends Biochem. Sci. 32, 530–531.

    PubMed  CAS  Google Scholar 

  68. von Mering, C., Krause, R., Snel, B., et al. (2002) Comparative assessment of large-scale data sets of protein-protein interactions. Nature 417, 399–403.

    Google Scholar 

  69. Yu, H., Braun, P., Yildirim, M. A., et al. (2008) High-quality binary protein interaction map of the yeast interactome network. Science 322, 104–110.

    PubMed  CAS  Google Scholar 

  70. Gavin, A. C., Aloy, P., Grandi, P., et al. (2006) Proteome survey reveals modularity of the yeast cell machinery. Nature 440, 631–636.

    PubMed  CAS  Google Scholar 

  71. Krogan, N. J., Cagney, G., Yu, H., et al. (2006) Global landscape of protein complexes in the yeast Saccharomyces cerevisiae. Nature 440, 637–643.

    PubMed  CAS  Google Scholar 

  72. Tarassov, K., Messier, V., Landry, C. R., et al. (2008) An in vivo map of the yeast protein interactome. Science 320, 1465–1470.

    PubMed  CAS  Google Scholar 

  73. Cusick, M. E., Klitgord, N., Vidal, M., and Hill, D. E. (2005) Interactome: gateway into systems biology. Hum. Mol. Genet. 14(Spec No. 2), R171-R181.

    PubMed  CAS  Google Scholar 

  74. Levy, E. D., Landry, C. R., and Michnick, S. W. (2009) How perfect can protein interactomes be? Sci. Signal. 2, pe11.

    Google Scholar 

  75. LaCount, D. J., Vignali, M., Chettier, R., et al. (2005) A protein interaction network of the malaria parasite Plasmodium falciparum. Nature 438, 103–107.

    PubMed  CAS  Google Scholar 

  76. Li, S., Armstrong, C. M., Bertin, N., et al. (2004) A map of the interactome network of the metazoan C. elegans. Science 303, 540–543.

    PubMed  CAS  Google Scholar 

  77. Simonis, N., Rual, J. F., Carvunis, A. R., et al. (2009) Empirically controlled mapping of the Caenorhabditis elegans protein-protein interactome network. Nat. Methods 6, 47–54.

    PubMed  CAS  Google Scholar 

  78. Giot, L., Bader, J. S., Brouwer, C., et al. (2003) A protein interaction map of Drosophila melanogaster. Science 302, 1727–1736.

    PubMed  CAS  Google Scholar 

  79. Rual, J. F., Venkatesan, K., Hao, T., et al. (2005) Towards a proteome-scale map of the human protein-protein interaction network. Nature 437, 1173–1178.

    PubMed  CAS  Google Scholar 

  80. Stelzl, U., Worm, U., Lalowski, M., et al. (2005) A human protein-protein interaction network: a resource for annotating the proteome. Cell 122, 957–968.

    PubMed  CAS  Google Scholar 

  81. Venkatesan, K., Rual, J. F., Vazquez, A., et al. (2009) An empirical framework for binary interactome mapping. Nat. Methods 6, 83–90.

    PubMed  CAS  Google Scholar 

  82. Bailer, S. M., and Haas, J. (2009) Connecting viral with cellular interactomes. Curr. Opin. Microbiol. 12, 453–459.

    PubMed  CAS  Google Scholar 

  83. Boxem, M., Maliga, Z., Klitgord, N., et al. (2008) A protein domain-based interactome network for C. elegans early embryogenesis. Cell 134, 534–545.

    PubMed  CAS  Google Scholar 

  84. Markson, G., Kiel, C., Hyde, R., et al. (2009) Analysis of the human E2 ubiquitin conjugating enzyme protein interaction network. Genome Res. 19, 1905–1911.

    PubMed  CAS  Google Scholar 

  85. Lim, J., Hao, T., Shaw, C., et al. (2006) A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration. Cell 125, 801–814.

    PubMed  CAS  Google Scholar 

  86. Ideker, T., and Sharan, R. (2008) Protein networks in disease. Genome Res. 18, 644–52.

    PubMed  CAS  Google Scholar 

  87. Hopkins, A. L., and Groom, C. R. (2002) The druggable genome. Nat. Rev. Drug Discov. 1, 727–730.

    PubMed  CAS  Google Scholar 

  88. Cochran, A. G. (2000) Antagonists of protein-protein interactions. Chem. Biol. 7, R85–R94.

    PubMed  CAS  Google Scholar 

  89. Domling, A. (2008) Small molecular weight protein-protein interaction antagonists: an insurmountable challenge? Curr. Opin. Chem. Biol. 12, 281–291.

    PubMed  CAS  Google Scholar 

  90. Colas, P. (2008) High-throughput screening assays to discover small-molecule inhibitors of protein interactions. Curr. Drug Discov. Technol. 5, 190–199.

    PubMed  CAS  Google Scholar 

  91. Bharucha, N., and Kumar, A. (2007) Yeast genomics and drug target identification. Comb. Chem. High Throughput Screen. 10, 618–634.

    PubMed  CAS  Google Scholar 

  92. Hoon, S., St. Onge, R. P., Giaever, G., and Nislow, C. (2008) Yeast chemical genomics and drug discovery: an update. Trends Pharmacol. Sci. 29, 499–504.

    PubMed  CAS  Google Scholar 

  93. Giaever, G., Shoemaker, D. D., Jones, T. W., et al. (1999) Genomic profiling of drug sensitivities via induced haploinsufficiency. Nat. Genet. 21, 278–283.

    PubMed  CAS  Google Scholar 

  94. Yan, Z., Costanzo, M., Heisler, L. E., et al. (2008) Yeast Barcoders: a chemogenomic application of a universal donor-strain collection carrying bar-code identifiers. Nat. Methods 5, 719–725.

    PubMed  CAS  Google Scholar 

  95. Ho, C. H., Magtanong, L., Barker, S. L., et al. (2009) A molecular barcoded yeast ORF library enables mode-of-action analysis of bioactive compounds. Nat. Biotechnol. 27, 369–377.

    PubMed  CAS  Google Scholar 

  96. Parsons, A. B., Brost, R. L., Ding, H., et al. (2004) Integration of chemical-genetic and genetic interaction data links bioactive compounds to cellular target pathways. Nat. Biotechnol. 22, 62–69.

    PubMed  CAS  Google Scholar 

  97. Yu, L., Lopez, A., Anaflous, A., et al. (2008) Chemical-genetic profiling of imidazo[1,2-a]pyridines and -pyrimidines reveals target pathways conserved between yeast and human cells. PLoS Genet. 4, e1000284.

    PubMed  Google Scholar 

  98. Rine, J., Hansen, W., Hardeman, E., and Davis, R. W. (1983) Targeted selection of recombinant clones through gene dosage effects. Proc. Natl. Acad. Sci. USA 80, 6750–6754.

    PubMed  CAS  Google Scholar 

  99. Armour, C. D., and Lum, P. Y. (2005) From drug to protein: using yeast genetics for high-throughput target discovery. Curr. Opin. Chem. Biol. 9, 20–24.

    PubMed  CAS  Google Scholar 

  100. Giaever, G. (2003) A chemical genomics approach to understanding drug action. Trends Pharmacol. Sci. 24, 444–446.

    PubMed  CAS  Google Scholar 

  101. Khozoie, C., Pleass, R. J., and Avery, S. V. (2009) The antimalarial drug quinine disrupts Tat2p-mediated tryptophan transport and causes tryptophan starvation. J. Biol. Chem. 284, 17968–17974.

    PubMed  CAS  Google Scholar 

  102. Li, W., Mo, W., Shen, D., et al. (2005) Yeast model uncovers dual roles of mitochondria in action of artemisinin. PLoS Genet. 1, e36.

    PubMed  Google Scholar 

  103. McCue, P. P., and Phang, J. M. (2008) Identification of human intracellular targets of the medicinal Herb St. John’s Wort by chemical-genetic profiling in yeast. J. Agric. Food Chem. 56, 11011–11017.

    PubMed  CAS  Google Scholar 

  104. Ericson, E., Gebbia, M., Heisler, L. E., et al. (2008) Off-target effects of psychoactive drugs revealed by genome-wide assays in yeast. PLoS Genet. 4, e1000151.

    PubMed  Google Scholar 

  105. Lesser, C. F., and Miller, S. I. (2001) Expression of microbial virulence proteins in Saccharomyces cerevisiae models mammalian infection. EMBO J. 20, 1840–1849.

    PubMed  CAS  Google Scholar 

  106. Siggers, K. A., and Lesser, C. F. (2008) The yeast Saccharomyces cerevisiae: a versatile model system for the identification and characterization of bacterial virulence proteins. Cell Host Microbe 4, 8–15.

    PubMed  CAS  Google Scholar 

  107. Curak, J., Rohde, J., and Stagljar, I. (2009) Yeast as a tool to study bacterial effectors. Curr. Opin. Microbiol. 12, 18–23.

    PubMed  CAS  Google Scholar 

  108. Zhang, M., Liang, Y., Zhang, X., Xu, Y., Dai, H., and Xiao, W. (2008) Deletion of yeast CWP genes enhances cell permeability to genotoxic agents. Toxicol. Sci. 103, 68–76.

    PubMed  CAS  Google Scholar 

  109. King, K., Dohlman, H. G., Thorner, J., Caron, M. G., and Lefkowitz, R. J. (1990) Control of yeast mating signal transduction by a mammalian beta 2-adrenergic receptor and Gs alpha subunit. Science 250, 121–123.

    PubMed  CAS  Google Scholar 

  110. Duport, C., Loeper, J., and Strosberg, A. D. (2003) Comparative expression of the human beta(2) and beta(3) adrenergic receptors in Saccharomyces cerevisiae. Biochim. Biophys. Acta 1629, 34–43.

    CAS  Google Scholar 

  111. Sander, P., Grunewald, S., Maul, G., Reilander, H., and Michel, H. (1994) Constitutive expression of the human D2S-dopamine receptor in the unicellular yeast Saccharomyces cerevisiae. Biochim. Biophys. Acta 1193, 255–262.

    PubMed  CAS  Google Scholar 

  112. Dirnberger, D., and Seuwen, K. (2007) Signaling of human frizzled receptors to the mating pathway in yeast. PLoS One 2, e954.

    PubMed  Google Scholar 

  113. Wedekind, A., O’Malley, M. A., Niebauer, R. T., and Robinson, A. S. (2006) Optimization of the human adenosine A2a receptor yields in Saccharomyces cerevisiae. Biotechnol. Prog. 22, 1249–1255.

    CAS  Google Scholar 

  114. Evans, B. J., Wang, Z., Broach, J. R., Oishi, S., Fujii, N., and Peiper, S. C. (2009) Expression of CXCR4, a n-coupled receptor for CXCL12 in yeast identification of new-generation inverse agonists. Methods Enzymol. 460, 399–412.

    PubMed  CAS  Google Scholar 

  115. Brown, A. J., Dyos, S. L., Whiteway, M. S., et al. (2000) Functional coupling of mammalian receptors to the yeast mating pathway using novel yeast/mammalian G protein alpha-subunit chimeras. Yeast 16, 11–22.

    PubMed  CAS  Google Scholar 

  116. Dowell, S. J., and Brown, A. J. (2009) Yeast assays for G protein-coupled receptors. Methods Mol. Biol. 552, 213–229.

    PubMed  CAS  Google Scholar 

  117. Ladds, G., Davis, K., Hillhouse, E. W., and Davey, J. (2003) Modified yeast cells to investigate the coupling of G protein-coupled receptors to specific G proteins. Mol. Microbiol. 47, 781–792.

    PubMed  CAS  Google Scholar 

  118. Niebauer, R. T., and Robinson, A. S. (2006) Exceptional total and functional yields of the human adenosine (A2a) receptor expressed in the yeast Saccharomyces cerevisiae. Protein Expr. Purif. 46, 204–211.

    PubMed  CAS  Google Scholar 

  119. Monk, B. C., and Cannon, R. D. (2002) Genomic pathways to antifungal discovery. Curr. Drug Targets Infect. Disord. 2, 309–329.

    PubMed  CAS  Google Scholar 

  120. Ma, D. (2001) Applications of yeast in drug discovery. Prog. Drug Res. 57, 117–162.

    PubMed  CAS  Google Scholar 

  121. Agarwal, A. K., Xu, T., Jacob, M. R., et al. (2008) Genomic and genetic approaches for the identification of antifungal drug targets. Infect. Disord. Drug Targets 8, 2–15.

    PubMed  CAS  Google Scholar 

  122. De Backer, M. D., and Van Dijck, P. (2003) Progress in functional genomics approaches to antifungal drug target discovery. Trends Microbiol. 11, 470–478.

    PubMed  Google Scholar 

  123. Balliano, G., Dehmlow, H., Oliaro-Bosso, S., et al. (2009) Oxidosqualene cyclase from Saccharomyces cerevisiae, Trypanosoma cruzi, Pneumocystis carinii and Arabidopsis thaliana expressed in yeast: a model for the development of novel antiparasitic agents. Bioorg. Med. Chem. Lett. 19, 718–723.

    PubMed  CAS  Google Scholar 

  124. Kim, Y. U., Ashida, H., Mori, K., Maeda, Y., Hong, Y., and Kinoshita, T. (2007) Both mammalian PIG-M and PIG-X are required for growth of GPI14-disrupted yeast. J. Biochem. 142, 123–129.

    PubMed  CAS  Google Scholar 

  125. Palmer, G., Louvion, J. F., Tibbetts, R. S., Engman, D. M., and Picard, D. (1995) Trypanosoma cruzi heat-shock protein 90 can functionally complement yeast. Mol. Biochem. Parasitol. 70, 199–202.

    PubMed  CAS  Google Scholar 

  126. Papageorgiou, I., De Koning, H. P., Soteriadou, K., and Diallinas, G. (2008) Kinetic and mutational analysis of the Trypanosoma brucei NBT1 nucleobase transporter expressed in Saccharomyces cerevisiae reveals structural similarities between ENT and MFS transporters. Int. J. Parasitol. 38, 641–653.

    PubMed  CAS  Google Scholar 

  127. Aguiar, P. H., Santos, D. N., Lobo, F. P., et al. (2006) Functional complementation of a yeast knockout strain by Schistosoma mansoni Rho1 GTPase in the presence of caffeine, an agent that affects mutants defective in the protein kinase C signal transduction pathway. Mem. Inst. Oswaldo Cruz 101(Suppl 1), 323–326.

    PubMed  Google Scholar 

  128. Santos, D. N., Aguiar, P. H., Lobo, F. P., et al. (2007) Schistosoma mansoni: Heterologous complementation of a yeast null mutant by SmRbx, a protein similar to a RING box protein involved in ubiquitination. Exp. Parasitol. 116, 440–449.

    PubMed  CAS  Google Scholar 

  129. Aruna, K., Chakraborty, T., Rao, P. N., Santos, C., Ballesta, J. P., and Sharma, S. (2005) Functional complementation of yeast ribosomal P0 protein with Plasmodium falciparum P0. Gene 357, 9–17.

    PubMed  CAS  Google Scholar 

  130. Djapa, L. Y., Basco, L. K., Zelikson, R., et al. (2007) Antifolate screening using yeast expressing Plasmodium vivax dihydrofolate reductase and in vitro drug susceptibility assay for Plasmodium falciparum. Mol. Biochem. Parasitol. 156, 89–92.

    PubMed  CAS  Google Scholar 

  131. Shams-Eldin, H., Azzouz, N., Kedees, M. H., Orlean, P., Kinoshita, T., and Schwarz, R. T. (2002) The GPI1 homologue from Plasmodium falciparum complements a Saccharomyces cerevisiae GPI1 anchoring mutant. Mol. Biochem. Parasitol. 120, 73–81.

    PubMed  CAS  Google Scholar 

  132. Wider, D., Peli-Gulli, M. P., Briand, P. A., Tatu, U., and Picard, D. (2009) The complementation of yeast with human or Plasmodium falciparum Hsp90 confers differential inhibitor sensitivities. Mol. Biochem. Parasitol. 164, 147–152.

    PubMed  CAS  Google Scholar 

  133. Birkholtz, L. M., Blatch, G., Coetzer, T. L., et al. (2008) Heterologous expression of plasmodial proteins for structural studies and functional annotation. Malar. J. 7, 197.

    PubMed  Google Scholar 

  134. LaCount, D. J., Schoenfeld, L. W., and Fields, S. (2009) Selection of yeast strains with enhanced expression of Plasmodium falciparum proteins. Mol. Biochem. Parasitol. 163, 119–122.

    PubMed  CAS  Google Scholar 

  135. Liu, R., Lin, Q., Sun, Y., et al. (2009) Expression, purification, and characterization of hepatitis B virus surface antigens (HBsAg) in yeast Pichia Pastoris. Appl. Biochem. Biotechnol. 158, 432–444.

    PubMed  CAS  Google Scholar 

  136. Bazan, S. B., de Alencar Muniz Chaves, A., Aires, K. A., Cianciarullo, A. M., Garcea, R. L., and Ho, P. L. (2009) Expression and characterization of HPV-16 L1 capsid protein in Pichia pastoris. Arch. Virol. 154, 1609–1617.

    PubMed  CAS  Google Scholar 

  137. Woo, M. K., An, J. M., Kim, J. D., Park, S. N., and Kim, H. J. (2008) Expression and purification of human papillomavirus 18 L1 virus-like particle from Saccharomyces cerevisiae. Arch. Pharm. Res. 31, 205–209.

    PubMed  CAS  Google Scholar 

  138. Etemad, B., Batra, G., Raut, et al. (2008) An envelope domain III-based chimeric antigen produced in Pichia pastoris elicits neutralizing antibodies against all four dengue virus serotypes. Am. J. Trop. Med. Hyg. 79, 353–363.

    PubMed  CAS  Google Scholar 

  139. Gerngross, T. U. (2004) Advances in the production of human therapeutic proteins in yeasts and filamentous fungi. Nat. Biotechnol. 22, 1409–1414.

    PubMed  CAS  Google Scholar 

  140. Akeboshi, H., Chiba, Y., Kasahara, Y., et al. (2007) Production of recombinant beta-hexosaminidase A, a potential enzyme for replacement therapy for Tay-Sachs and Sandhoff diseases, in the methylotrophic yeast Ogataea minuta. Appl. Environ. Microbiol. 73, 4805–4812.

    PubMed  CAS  Google Scholar 

  141. Chen, Y., Jin, M., Egborge, T., Coppola, G., Andre, J., and Calhoun, D. H. (2000) Expression and characterization of glycosylated and catalytically active recombinant human alpha-galactosidase A produced in Pichia pastoris. Protein Expr. Purif. 20, 472–484.

    PubMed  CAS  Google Scholar 

  142. Chiba, Y., Sakuraba, H., Kotani, M., et al. (2002) Production in yeast of alpha-galactosidase A, a lysosomal enzyme applicable to enzyme replacement therapy for Fabry disease. Glycobiology 12, 821–828.

    PubMed  CAS  Google Scholar 

  143. Sakuraba, H., Chiba, Y., Kotani, M., et al. (2006) Corrective effect on Fabry mice of yeast recombinant human alpha-galactosidase with N-linked sugar chains suitable for lysosomal delivery. J. Hum. Genet. 51, 341–352.

    PubMed  CAS  Google Scholar 

  144. Chiba, Y., and Akeboshi, H. (2009) Glycan engineering and production of ’humanized’ glycoprotein in yeast cells. Biol. Pharm. Bull. 32, 786–795.

    PubMed  CAS  Google Scholar 

  145. Abe, H., Takaoka, Y., Chiba, Y., et al. (2009) Development of valuable yeast strains using a novel mutagenesis technique for the effective production of therapeutic glycoproteins. Glycobiology 19, 428–436.

    PubMed  CAS  Google Scholar 

  146. Graf, A., Dragosits, M., Gasser, B., and Mattanovich, D. (2009) Yeast systems biotechnology for the production of heterologous proteins. FEMS Yeast Res. 9, 335–348.

    PubMed  CAS  Google Scholar 

  147. Hamilton, S. R., and Gerngross, T. U. (2007) Glycosylation engineering in yeast: the advent of fully humanized yeast. Curr. Opin. Biotechnol. 18, 387–392.

    PubMed  CAS  Google Scholar 

  148. Rakestraw, J. A., Sazinsky, S. L., Piatesi, A., Antipov, E., and Wittrup, K. D. (2009) Directed evolution of a secretory leader for the improved expression of heterologous proteins and full-length antibodies in Saccharomyces cerevisiae. Biotechnol. Bioeng. 103, 1192–1201.

    PubMed  CAS  Google Scholar 

  149. Schirrmann, T., Al-Halabi, L., Dubel, S., and Hust, M. (2008) Production systems for recombinant antibodies. Front. Biosci. 13, 4576–4594.

    PubMed  CAS  Google Scholar 

  150. Takegawa, K., Tohda, H., Sasaki, M., et al. (2009) Production of heterologous proteins using the fission-yeast (Schizosaccharomyces pombe) expression system. Biotechnol. Appl. Biochem. 53, 227–235.

    PubMed  CAS  Google Scholar 

  151. Wildt, S., and Gerngross, T. U. (2005) The humanization of N-glycosylation pathways in yeast. Nat. Rev. Microbiol. 3, 119–128.

    PubMed  CAS  Google Scholar 

  152. Wiseman, A. (2004) Double humanized yeast makes hydrocortisone. Trends Biotechnol. 22, 324–325.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry, Cambridge Systems Biology Centre, University of Cambridge, Cambridge, UK

    Nianshu Zhang & Elizabeth Bilsland

Authors
  1. Nianshu Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elizabeth Bilsland
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nianshu Zhang .

Editor information

Editors and Affiliations

  1. , Department of Biochemistry, University of Cambridge, Tennis Court Road 80, Cambridge, CB2 1GA, United Kingdom

    Juan I. Castrillo

  2. , Department of Biochemistry, University of Cambridge, Tennis Court Road 80, Cambridge, CB2 1GA, United Kingdom

    Stephen G. Oliver

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Humana Press

About this protocol

Cite this protocol

Zhang, N., Bilsland, E. (2011). Contributions of Saccharomyces cerevisiae to Understanding Mammalian Gene Function and Therapy. In: Castrillo, J., Oliver, S. (eds) Yeast Systems Biology. Methods in Molecular Biology, vol 759. Humana Press. https://doi.org/10.1007/978-1-61779-173-4_28

Download citation

  • DOI: https://doi.org/10.1007/978-1-61779-173-4_28

  • Published:

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-61779-172-7

  • Online ISBN: 978-1-61779-173-4

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation