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The Fungal Metabolite Brefeldin A Inhibits Dvl2-Plk1-Dependent Primary Cilium Disassembly

  • Lee, Uijeong (World Class Institute (WCI), Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Kim, Sun-Ok (World Class Institute (WCI), Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Hwang, Jeong-Ah (World Class Institute (WCI), Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Jang, Jae-Hyuk (World Class Institute (WCI), Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Son, Sangkeun (World Class Institute (WCI), Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Ryoo, In-Ja (World Class Institute (WCI), Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Ahn, Jong Seog (World Class Institute (WCI), Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Kim, Bo Yeon (World Class Institute (WCI), Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Lee, Kyung Ho (World Class Institute (WCI), Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB))
  • Received : 2017.03.03
  • Accepted : 2017.05.11
  • Published : 2017.06.30

Abstract

The primary cilium is a non-motile microtubule-based organelle that protrudes from the surface of most human cells and works as a cellular antenna to accept extracellular signals. Primary cilia assemble from the basal body during the resting stage ($G_0$ phase) and simultaneously disassemble with cell cycle re-entry. Defective control of assembly or disassembly causes diverse human diseases including ciliopathy and cancer. To identify the effective compounds for studying primary cilium disassembly, we have screened 297 natural compounds and identified 18 and 17 primary cilium assembly and disassembly inhibitors, respectively. Among them, the application of KY-0120, identified as Brefeldin A, disturbed Dvl2-Plk1-mediated cilium disassembly via repression of the interaction of $CK1{\varepsilon}-Dvl2$ and the expression of Plk1 mRNA. Therefore, our study may suggest useful compounds for studying the cellular mechanism of primary cilium disassembly to prevent ciliopathy and cancer.

Keywords

brefeldin A;Dvl2;inhibitor;Plk1;primary cilium disassembly

Acknowledgement

Supported by : KRIBB, NST (National Research Council of Science & Technology) of Republic of Korea

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