The Fungal Metabolite Brefeldin A Inhibits Dvl2- Plk1-Dependent Primary Cilium Disassembly
Uijeong Lee1,2,4, Sun-Ok Kim1,4, Jeong-Ah Hwang1,3,4, Jae-Hyuk Jang1,2, Sangkeun Son1,2, In-Ja Ryoo1, Jong Seog Ahn1,2, Bo Yeon Kim1,2,* , and Kyung Ho Lee1,*
1World Class Institute (WCI), Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Chungbuk 28116, Korea, 2Department of Biomolecular Science, University of Science and Technology, Daejeon 34113, Korea, 3Research Institute of Medical Sciences, Department of Physiology, College of Medicine, Chungnam National University, Daejeon 34134, Korea, 4These authors contributed equally to this work.
*Correspondence: leekh@kribb.re.kr (KHL); bykim@kribb.re.kr (BYK)
Received March 3, 2017; Revised April 28, 2017; Accepted May 11, 2017.; Published online June 14, 2017.
© Korean Society for Molecular and Cellular Biology. All rights reserved.

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit (http://creativecommons.org/licenses/by-nc-sa/3.0/).
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 (G0 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 CK1e-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


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31 May 2017 Volume 40,
Number 5, pp. 315~378

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