Use of yeast as a model system for identifying and studying anticancer drugs

As signified in part by the publication of the current book, yeast is becoming a more widely used system for studying small molecule-protein interactions in general and anticancer agents in particular. There are a number of reasons for this surging popularity. As a eukaryote, it contains many, if not most, of the essential genes involved in the control of cell cycle, cellular structure, metabolism, and stress responses that are conserved from yeast to humans, making it possible to use yeast to study the function of those genes. For this reason, what is learned in a yeast cell can often been extrapolated into a mammalian counterpart. Unlike mammalian cells, yeast is relatively easy to grow and manipulate, with its natural habitat being the harsh environment of the wild. Moreover, decades of research on both the biochemistry and genetics of the budding yeast has accumulated a wealth of information about yeast and made available a number of tools that allows for the manipulation of genes in yeast, including knockout and ectopic expression of both endogenous and exogenous genes. Several recent advances have greatly facilitated the use of yeast as a powerful system to study small molecules. They include the advent of the yeast two-hybrid system, the sequencing of the genome of the budding yeast Saccharomyces cerevisiae and the development of DNA chip and microarrays that allow for the monitoring of the expression of the complete yeast genome. In this chapter, we will cover three different ways yeast has been used to facilitate the identification, characterization, and mechanistic studies of anticancer drugs. These include (1) the use of yeast as a surrogate system to identify and study anticancer drugs; (2) the use of yeast as selfcontained microvessles to perform large-scale parallel analysis of interactions between proteins and small ligands; and (3) the use of the yeast transcriptional profiling for validating the molecular target for given drugs. For the most part, we have selected examples from our own laboratories. We thus have attempted to be more illustrative than comprehensive in this chapter.