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KMID : 0545120080180020263
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Journal of Microbiology and Biotechnology
2008 Volume.18 No. 2 p.263 ~ p.269
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Genome-wide Drug-induced Haploinsufficient Screening of Fission Yeast for Identification of Hydrazinocurcumin Targets
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Baek Seung-Tae
Kim Dong-Uk
Han Sang-Jo
Woo Im-Sun
Nam Mi-Young
Kim Lil-A
Heo Kyung-Sun
Lee Hye-Mi
Hwang Hye-Rim
Choi Shin-Jung
Won Mi-Sun
Lee Min-Ho
Park Song-Kyu
Lee Sung-Hou
Kwon Ho-Jeong
Maeng Pil-Jae
Park Hee-Moon
Park Young-Woo
Kim Dong-Sup
Hoe Kwang-Lae
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Abstract
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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 genomewide 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 (IC50) 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 acetyl transferase. The target mutants showed 65% growth inhibition in response to HC compared with wild-type controls, as shown by liquid culture assay.
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KEYWORD
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Haploinsufficiency, hydrazinocurcumin, septin, taf4, yeast
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