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Title 

Genome-wide drug-induced haploinsufficiency screening of fission yeast for identification of hydrazinocurcumin targets

Authors 

Seung-Tae BaekDong Uk KimS HanI S WooMiyoung NamL KimKyung Sun HeoHye Mi LeeH R HwangShin Jung ChoiMi Sun WonM LeeSong Kyu ParkS LeeH J KwonP J MaengH M ParkYoung Woo ParkD KimKwang Lae Hoe

Publisher 

The Korean Society for Applied Microbiology

Issue Date 

2008

Citation 

Journal of Microbiology and Biotechnology, vol. 18, no. 2, pp. 263-269

Keywords 

haploinsufficiencyhydrazinocurcuminseptintaf4 yeastdrug derivativedrug sensitivitydrug targetinggenetic screeninggenomeyeast

Abstract 

Hydrazinocurcumin (HC), a synthetic derivative of curcumin, has been reported to inhibit angiogenesis via unknown mechanisms. Understanding the molecular mechanisms of the drug's action is important for the development of improved compounds with better pharmacological properties. A genome-wide drug-induced haploinsufficiency screening of fission yeast gene deletion mutants has been applied to identify drug targets of HC. As a first step, the 50% inhibition concentration (IG50) of HC was determined to be 2.2 μM. The initial screening of 4,158 mutants in 384-well plates using robotics was performed at concentrations of 2,3, and 4 μM. A second screening was performed to detect sensitivity to HC on the plates. The first screening revealed 178 candidates, and the second screening resulted in 13 candidates, following the elimination of 165 false positives. Final filtering of the condition-dependent haploinsufficient genes gave eight target genes. Analysis of the specific targets of HC has shown that they are related to septum formation and the general transcription processes, which may be related to histone acetyltransferase. The target mutants showed 65% growth inhibition in response to HC compared with wild-type controls, as shown by liquid culture assay.

ISSN 

1017-7825

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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