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Budding actors in mammalian G-protein signaling

Nature Biotechnology volume 17, pages 852–853 (1999)Cite this article

The domestication of budding yeast (Saccharomyces cerevisiae) for the production of alcoholic beverages and for use as leavening is one of the earliest known examples of biotechnology. Humankind's early interest in this organism is partly responsible for the intense study of its biochemistry and genetics, and S. cerevisiae has since become a classic model system for studies in molecular genetics and cell biology. This "simple" prototype for the eukaryotic cell is increasingly being exploited as a tool in biotechnology to determine function for newly sequenced mammalian genes and to identify new drug candidates and targets. In this issue, Cismowski et al.1 describe genetic screens in yeast to identify human genes whose products can modulate the activity of an important class of mammalian signaling proteins, the heterotrimeric G proteins.

Our capacity to sequence genomes has greatly outpaced our ability to assign function to the genes they encode. This problem has spurred the development of a number of scalable experimental strategies collectively referred to as "functional genomics." Computational approaches2, homology searches, and structural genomics3 aim to infer function for gene sequences based on the identification of known signature domains or folds that they encode, but can neither predict nor identify novel activities. Moreover, proteins with similar structures or domains can play very different roles in the cell. "Guilt by association" techniques, such as the yeast two-hybrid and related assays4,5 and gene expression profiling6, provide very strong clues to, but fall short of directly identifying, gene function. A complementary approach is to use screens in model organisms to directly assay genes for defined functions. The ease and low cost of genetic manipulation in yeast, the functional complementarity of many yeast proteins with orthologs in higher eukaryotes, and our detailed understanding of yeast biology have made it an ideal medium for the development of these strategies.

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Figure 1: Genetic screen in yeast to identify modulators of mammalian G-protein signaling.

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  1. Research Editor at Nature Biotechnology, Nature America, Inc., New York, 10010, NY

    Robert M. Frederickson

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  1. Robert M. Frederickson
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Frederickson, R. Budding actors in mammalian G-protein signaling. Nat Biotechnol 17, 852–853 (1999). https://doi.org/10.1038/12837

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