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

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Title
Genome-wide drug-induced haploinsufficiency screening of fission yeast for identification of hydrazinocurcumin targets
Author(s)
Seung-Tae Baek; Dong Uk Kim; S Han; I S Woo; Miyoung Nam; L Kim; Kyung Sun Heo; Hye Mi Lee; H R Hwang; Shin Jung Choi; Mi Sun Won; M Lee; Song Kyu Park; S Lee; H J Kwon; P J Maeng; H M Park; Young Woo Park; D Kim; Kwang Lae Hoe
Bibliographic Citation
Journal of Microbiology and Biotechnology, vol. 18, no. 2, pp. 263-269
Publication Year
2008
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.
Keyword
haploinsufficiencyhydrazinocurcuminseptintaf4 yeast
ISSN
1017-7825
Publisher
South Korea
Type
Article
Appears in Collections:
Division of Biomedical Research > Rare Disease Research Center > 1. Journal Articles
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
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