Lee Uijeong, Kim Sun-Ok, Hwang Jeong-Ah, Jang Jae-Hyuk, Son Sangkeun, Ryoo In-Ja, Ahn Jong Seog, Kim Bo Yeon, Lee Kyung Ho
World Class Institute (WCI), Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Chungbuk 28116, Korea.
Department of Biomolecular Science, University of Science and Technology, Daejeon 34113, Korea.
Mol Cells. 2017 Jun 30;40(6):401-409. doi: 10.14348/molcells.2017.0032. Epub 2017 Jun 14.
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 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 CK1ɛ-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.
初级纤毛是一种基于微管的非运动性细胞器，从大多数人类细胞表面突出，作为细胞天线接受细胞外信号。初级纤毛在静止期（G期）从基体组装而成，并在细胞周期重新进入时同时解体。组装或解体的控制缺陷会导致包括纤毛病和癌症在内的多种人类疾病。为了鉴定用于研究初级纤毛解体的有效化合物，我们筛选了297种天然化合物，分别鉴定出18种和17种初级纤毛组装和解体抑制剂。其中，被鉴定为布雷菲德菌素A的KY-0120的应用，通过抑制CK1ɛ-Dvl2的相互作用和Plk1 mRNA的表达，干扰了Dvl2-Plk1介导的纤毛解体。因此，我们的研究可能为研究初级纤毛解体的细胞机制以预防纤毛病和癌症提供有用的化合物。
