Scientific Publications

Microarray-based method for monitoring yeast overexpression strains reveals small-molecule targets in TOR pathway.

Publication TypeJournal Article
AuthorsButcher, RA, Bhullar BS, Perlstein EO, Marsischky G., LaBaer J., and Schreiber SL
AbstractIdentification of the cellular targets of small-molecule hits in phenotypic screens is a central challenge in the development of small molecules as biological tools and potential therapeutics. To facilitate the process of small-molecule target identification, we developed a global, microarray-based method for monitoring the growth of pools of yeast strains, each overexpressing a different protein, in the presence of small molecules. Specifically, the growth of Saccharomyces cerevisiae strains harboring approximately 3,900 different overexpression plasmids was monitored in the presence of rapamycin, which inhibits the target of rapamycin (TOR) proteins. TOR was successfully identified as a candidate rapamycin target, and many additional gene products were implicated in the TOR signaling pathway. We also characterized the mechanism of LY-83583, a small-molecule suppressor of rapamycin-induced growth inhibition. These data enabled functional links to be drawn between groups of genes implicated in the TOR pathway, identified several candidate targets for LY-83583, and suggested a role for mitochondrial respiration in mediating rapamycin sensitivity.
Year of Publication2006
JournalNature chemical biology
Volume2
Issue2
Pages103-9
Date Published (YYYY/MM/DD)2006/02/01
ISSN Number1552-4450
DOI10.1038/nchembio762
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/16415861?dopt=Abstract