Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Genome-wide Drug-induced Haploinsufficiency Screening of Fission Yeast for Identification of Hydrazinocurcumin Targets

  • Baek, Seung-Tae (Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology(KRIBB)) ;
  • Kim, Dong-Uk (Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology(KRIBB)) ;
  • Han, Sang-Jo (Department of Bio and Brain Engineeering, Korea Advanced Institute of Science and Technology(KAIST)) ;
  • Woo, Im-Sun (Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology(KRIBB)) ;
  • Nam, Mi-Young (Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology(KRIBB)) ;
  • Kim, Li-La (Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology(KRIBB)) ;
  • Heo, Kyung-Sun (Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology(KRIBB)) ;
  • Lee, Hye-Mi (Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology(KRIBB)) ;
  • Hwang, Hye-Rim (Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology(KRIBB)) ;
  • Choi, Shin-Jung (Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology(KRIBB)) ;
  • Won, Mi-Sun (Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology(KRIBB)) ;
  • Lee, Min-Ho (Department of Bio and Brain Engineeering, Korea Advanced Institute of Science and Technology(KAIST)) ;
  • Park, Song-Kyu (Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology(KRIBB)) ;
  • Lee, Sung-Hou (Department of Biotechnology and Informatics, Sangmyung University) ;
  • Kwon, Ho-Jeong (Department of Biotechnology, Yonsei University) ;
  • Maeng, Pil-Jae (Department of Microbiology, School of Biological Science and Biotechnology, Chungnam National University) ;
  • Park, Hee-Moon (Department of Microbiology, School of Biological Science and Biotechnology, Chungnam National University) ;
  • Park, Young-Woo (Therapeutic Antibody Research Center, Korea Research Institute of Bioscience and Biotechnology(KRIBB)) ;
  • Kim, Dong-Sup (Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST)) ;
  • Hoe, Kwang-Lae (Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB))
  • Published : 2008.02.29
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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 $(IC_{50})$ of HC was determined to be $2.2{\mu}M$. The initial screening of 4,158 mutants in 384-well plates using robotics was performed at concentrations of 2, 3, and $4{\mu}M$. 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.

Keywords

References

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