한빛사논문
- 조회1,785
Abstract
Kyung Ho Lee1,6, Yoshikazu Johmura1, Li-Rong Yu2, Jung-Eun Park1, Yuan Gao2, Jeong K Bang3, Ming Zhou4, Timothy D Veenstra4, Bo Yeon Kim5 and Kyung S Lee1,*
1Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
2Division of Systems Biology, Center for Proteomics, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA
3Division of Magnetic Resonance, Korea Basic Science Institute, Chung-Buk, Republic of Korea
4Laboratory of Proteomics and Analytical Technologies, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA
5Chemical Biology Research Center and World Class Institute, Korea Research Institute of Bioscience and Biotechnology, Chung-Buk, Republic of Korea
*Correspondence to:
Kyung S Lee, Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute/NIH, 9000 Rockville Pike, Building 37, Room 3118, Bethesda, MD 20892-4258, USA.
6Present address: Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology, Republic of Korea
Non-motile primary cilium is an antenna-like structure whose defect is associated with a wide range of pathologies, including developmental disorders and cancer. Although mechanisms regulating cilia assembly have been extensively studied, how cilia disassembly is regulated remains poorly understood. Here, we report unexpected roles of Dishevelled 2 (Dvl2) and interphase polo-like kinase 1 (Plk1) in primary cilia disassembly. We demonstrated that Dvl2 is phosphorylated at S143 and T224 in a manner that requires both non-canonical Wnt5a ligand and casein kinase 1 epsilon (CK1ε), and that this event is critical to interact with Plk1 in early stages of the cell cycle. The resulting Dvl2-Plk1 complex mediated Wnt5a-CK1ε-Dvl2-dependent primary cilia disassembly by stabilizing the HEF1 scaffold and activating its associated Aurora-A (AurA), a kinase crucially required for primary cilia disassembly. Thus, via the formation of the Dvl2-Plk1 complex, Plk1 plays an unanticipated role in primary cilia disassembly by linking Wnt5a-induced biochemical steps to HEF1/AurA-dependent cilia disassembly. This study may provide new insights into the mechanism underlying ciliary disassembly processes and various cilia-related disorders.
Keywords:Cilia; CK1; Dvl2; Plk1; Wnt
논문정보
- Research article
- 2012년 05월 (BRIC 등록일 )
- 국내+국외 연구진
- 생명과학 > 분자생물학
댓글 작성 로그인
팝업 닫기관련 링크
연구자 키워드
연구자 ID
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기
