Yeast genome-wide drug-induced haploinsufficiency screen to determine drug mode of action.
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.
Baetz
Kristin
K
Centre for Molecular Medicine and Therapeutics, Vancouver, BC, Canada V5Z 4H4.
McHardy
Lianne
L
Gable
Ken
K
Tarling
Tamsin
T
Rebérioux
Delphine
D
Bryan
Jenny
J
Andersen
Raymond J
RJ
Dunn
Teresa
T
Hieter
Phil
P
Roberge
Michel
M
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
D000935:Antifungal Agents; D013107:Sphingolipids