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The yeast two-hybrid assay: still finding connections after 25 years

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The idea of using hybrid proteins containing transcription factor domains to analyze protein-protein interactions was described in 1989. Over the past 25 years, this method has begun to reveal the complex protein networks that underlie cellular behavior.

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Figure 1: A human reference interactome by 2020? (a) The invention of the yeast two-hybrid assay sparked the idea that protein-protein interaction networks should and could be mapped, as shown here for Saccharomyces cerevisiae and Caenorhabditis elegans.

References

  1. Fields, S. & Song, O. Nature 340, 245–246 (1989).

    Article  CAS  Google Scholar 

  2. Chien, C.T., Bartel, P.L., Sternglanz, R. & Fields, S. Proc. Natl. Acad. Sci. USA 88, 9578–9582 (1991).

    Article  CAS  Google Scholar 

  3. Vidal, M. & Legrain, P. Nucleic Acids Res. 27, 919–929 (1999).

    Article  CAS  Google Scholar 

  4. Li, J.J. & Herskowitz, I. Science 262, 1870–1874 (1993).

    Article  CAS  Google Scholar 

  5. Wang, M.M. & Reed, R.R. Nature 364, 121–126 (1993).

    Article  CAS  Google Scholar 

  6. SenGupta, D.J. et al. Proc. Natl. Acad. Sci. USA 93, 8496–8501 (1996).

    Article  CAS  Google Scholar 

  7. Licitra, E.J. & Liu, J.O. Proc. Natl. Acad. Sci. USA 93, 12817–12821 (1996).

    Article  CAS  Google Scholar 

  8. Johnsson, N. & Varshavsky, A. Proc. Natl. Acad. Sci. USA 91, 10340–10344 (1994).

    Article  CAS  Google Scholar 

  9. Pelletier, J.N., Campbell-Valois, F.X. & Michnick, S.W. Proc. Natl. Acad. Sci. USA 95, 12141–12146 (1998).

    Article  CAS  Google Scholar 

  10. Eyckerman, S. et al. Nat. Cell Biol. 3, 1114–1119 (2001).

    Article  CAS  Google Scholar 

  11. Ramachandran, N. et al. Science 305, 86–90 (2004).

    Article  CAS  Google Scholar 

  12. Vidal, M., Brachmann, R.K., Fattaey, A., Harlow, E. & Boeke, J.D. Proc. Natl. Acad. Sci. USA 93, 10315–10320 (1996).

    Article  CAS  Google Scholar 

  13. Dreze, M. et al. Nat. Methods 6, 843–849 (2009).

    Article  CAS  Google Scholar 

  14. Oliver, S.G. et al. Nature 357, 38–46 (1992).

    Article  CAS  Google Scholar 

  15. Sulston, J. et al. Nature 356, 37–41 (1992).

    Article  Google Scholar 

  16. Bartel, P.L., Roecklein, J.A., SenGupta, D. & Fields, S. Nat. Genet. 12, 72–77 (1996).

    Article  CAS  Google Scholar 

  17. Fromont-Racine, M., Rain, J.C. & Legrain, P. Nat. Genet. 16, 277–282 (1997).

    Article  CAS  Google Scholar 

  18. Walhout, A.J. & Vidal, M. Genome Res. 9, 1128–1134 (1999).

    Article  CAS  Google Scholar 

  19. Uetz, P. et al. Nature 403, 623–627 (2000).

    Article  CAS  Google Scholar 

  20. Ito, T. et al. Proc. Natl. Acad. Sci. USA 98, 4569–4574 (2001).

    Article  CAS  Google Scholar 

  21. Walhout, A.J. et al. Science 287, 116–122 (2000).

    Article  CAS  Google Scholar 

  22. Li, S. et al. Science 303, 540–543 (2004).

    Article  CAS  Google Scholar 

  23. Giot, L. et al. Science 302, 1727–1736 (2003).

    Article  CAS  Google Scholar 

  24. Rual, J.-F. et al. Nature 437, 1173–1178 (2005).

    Article  CAS  Google Scholar 

  25. Stelzl, U. et al. Cell 122, 957–968 (2005).

    Article  CAS  Google Scholar 

  26. Gavin, A.C. et al. Nature 415, 141–147 (2002).

    Article  CAS  Google Scholar 

  27. Gavin, A.C. et al. Nature 440, 631–636 (2006).

    Article  CAS  Google Scholar 

  28. Ho, Y. et al. Nature 415, 180–183 (2002).

    Article  CAS  Google Scholar 

  29. Krogan, N.J. et al. Nature 440, 637–643 (2006).

    Article  CAS  Google Scholar 

  30. Rolland, T. et al. Cell (in the press).

  31. Venkatesan, K. et al. Nat. Methods 6, 83–90 (2009).

    Article  CAS  Google Scholar 

  32. Ge, H., Walhout, A.J. & Vidal, M. Trends Genet. 19, 551–560 (2003).

    Article  CAS  Google Scholar 

  33. Han, J.D. et al. Nature 430, 88–93 (2004).

    Article  CAS  Google Scholar 

  34. Gu, L. et al. Nature doi:10.1038/nature13761 (21 September 2014).

Download references

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Correspondence to Marc Vidal or Stanley Fields.

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Vidal, M., Fields, S. The yeast two-hybrid assay: still finding connections after 25 years. Nat Methods 11, 1203–1206 (2014). https://doi.org/10.1038/nmeth.3182

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