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

نویسندگان

  • Uijeong Lee
  • Sun-Ok Kim
  • Jeong-Ah Hwang
  • Jae-Hyuk Jang
  • Sangkeun Son
  • In-Ja Ryoo
  • Jong Seog Ahn
  • Bo Yeon Kim
  • Kyung Ho Lee
چکیده

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 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.

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عنوان ژورنال:

دوره 40  شماره 

صفحات  -

تاریخ انتشار 2017