title: Yeast genome-wide drug-induced haploinsufficiency screen to determine drug mode of action.
abstract: Methods to systematically test drugs against all possible proteins in a cell are needed to identify the targets underlying their therapeutic action and unwanted effects. Here, we show that a genome-wide drug-induced haploinsufficiency screen by using yeast can reveal drug mode of action in yeast and can be used to predict drug mode of action in human cells. We demonstrate that dihydromotuporamine C, a compound in preclinical development that inhibits angiogenesis and metastasis by an unknown mechanism, targets sphingolipid metabolism. The systematic, unbiased and genome-wide nature of this technique makes it attractive as a general approach to identify cellular pathways affected by drugs.
authors.affiliation: Centre for Molecular Medicine and Therapeutics, Vancouver, BC, Canada V5Z 4H4.
authors.forename: Kristin
authors.initials: K
authors.lastname: Baetz
authors.forename: Lianne
authors.initials: L
authors.lastname: McHardy
authors.forename: Ken
authors.initials: K
authors.lastname: Gable
authors.forename: Tamsin
authors.initials: T
authors.lastname: Tarling
authors.forename: Delphine
authors.initials: D
authors.lastname: Rebérioux
authors.forename: Jenny
authors.initials: J
authors.lastname: Bryan
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Andersen
authors.forename: Teresa
authors.initials: T
authors.lastname: Dunn
authors.forename: Phil
authors.initials: P
authors.lastname: Hieter
authors.forename: Michel
authors.initials: M
authors.lastname: Roberge
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D017353:Gene Deletion; D016681:Genome, Fungal; D008826:Microbial Sensitivity Tests; D011003:Ploidies; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics*; D017384:Sequence Deletion; D015398:Signal Transduction; D013107:Sphingolipids / Q000096:biosynthesis
chemical_list: D000935:Antifungal Agents; D013107:Sphingolipids