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

Seung Tae Baek, Dong Uk Kim, Sangjo Han, Im Sun Woo, Miyoung Nam, Lila Kim, Kyung Sun Heo, Hyemi Lee, Hye Rim Hwang, Shin Jung Choi, Misun Won, Minho Lee, Song Kyu Park, Sunghou Lee, Ho Jeong Kwon, Pil Jae Maeng, Hee Moon Park, Youngwoo Park, Dongsup Kim, Kwang Lae Hoe

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6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)263-269
Number of pages7
JournalJournal of microbiology and biotechnology
Volume18
Issue number2
Publication statusPublished - 2008 Feb 28

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Applied Microbiology and Biotechnology

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    Baek, S. T., Kim, D. U., Han, S., Woo, I. S., Nam, M., Kim, L., Heo, K. S., Lee, H., Hwang, H. R., Choi, S. J., Won, M., Lee, M., Park, S. K., Lee, S., Kwon, H. J., Maeng, P. J., Park, H. M., Park, Y., Kim, D., & Hoe, K. L. (2008). Genome-wide drug-induced haploinsufficient screening of fission yeast for identification of hydrazinocurcumin targets. Journal of microbiology and biotechnology, 18(2), 263-269.