Abstract
The two-hybrid system dates to early 1987, when Stanley Fields was a new assistant professor at the State University of New York at Stony Brook with a small National Science Foundation grant. The university had a seed grant program to fund ideas with commercial potential, and it struck us that we would be more likely to obtain such a grant than another federal grant. Unfortunately, the laboratory was working on pheromone response in the yeast Saccharomyces cerevisiae, in particular the role of a protein implicated in transcriptional induction, and the intricacies of yeast mating behavior seemed unlikely to excite the seed grant panel. However, our research interests kept us familiar with the current findings in transcriptional regulation. Specifically, we knew of two key results: one was the work of Brent and Ptashne (1) demonstrating that a hybrid transcriptional activator could be generated from the E. coli LexA repressor and the yeast Gal4 protein; the second was the work of groups such as Triezenberg et al. (2) suggesting that transcriptional activators could function by binding to DNA-bound proteins rather than directly to DNA. We toyed with various notions in the hope of linking yeast transcription to commercial potential. Late one afternoon, the idea came to use two different hybrid proteins, one containing a DNA-binding domain and one a transcriptional activation domain (AD), to detect protein-protein interactions. Thus was born the two-hybrid system, not as an incremental step in our continuing studies but in an instant.
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References
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Fields, S., Bartel, P.L. (2001). The Two-Hybrid System. In: MacDonald, P.N. (eds) Two-Hybrid Systems. Methods in Molecular Biology, vol 177. Humana Press. https://doi.org/10.1385/1-59259-210-4:003
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DOI: https://doi.org/10.1385/1-59259-210-4:003
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