Yeast genome-wide drug-induced haploinsufficiency screen to determine drug mode of action

Authors

• Kristin Baetz, Centre for Molecular Medicine and Therapeutics
• Lianne McHardy, University of British Columbia
• Ken Gable, Uniformed Services University of the Health Sciences
• Tamsin Tarling, University of British Columbia
• Delphine Rebérioux, University of British Columbia
• Jenny Bryan, University of British Columbia
• Raymond J. Andersen, University of British Columbia
• Teresa Dunn, Uniformed Services University of the Health Sciences
• Phil Hieter, University of British Columbia
• Michel Roberge, University of British ColumbiaFollow

Date of this Version

2004

Comments

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.

Abstract

Published in PNAS (2004) 101(13): pp. 4525-4530; doi:10.1073/pnas.0307122101