Cep131 overexpression promotes centrosome amplification and colon cancer progression by regulating Plk4 stability
- 주제(기타) Cell Biology
- 설명문(일반) [Kim, Dong Hyun; Ahn, Jong Seog; Han, Ho Jin; Kim, Hye-Min; Hwang, Joonsung; Lee, Kyung Ho; Cha-Molstad, Hyunjoo; Ryoo, In-Ja; Jang, Jae-Hyuk; Ko, Sung-Kyun; Lee, Sangku; Soung, Nak-Kyun; Kim, Bo Yeon] Korea Res Inst Biosci & Biotechnol, Anticanc Agent Res Ctr, Ochang 28116, Cheongju, South Korea; [Kim, Dong Hyun; Ahn, Jong Seog; Han, Ho Jin; Jang, Jae-Hyuk; Ko, Sung-Kyun; Soung, Nak-Kyun; Kim, Bo Yeon] Univ Sci & Technol, Dept Biomol Sci, Daejeon 34113, South Korea; [Yang, Jin Ok] Korea Res Inst Biosci & Biotechnol, Korean Bioinformat Ctr, Daejeon 34141, South Korea; [Lee, Hee Gu] Korea Res Inst Biosci & Biotechnol, Immunotherapy Convergence Res Ctr, Daejeon 34141, South Korea; [Song, Eun Joo] Korea Inst Sci & Technol, Mol Recognit Res Ctr, Seoul 02792, South Korea; [Kim, Jin Young] Korea Basic Sci Inst, Biomed Omics Res, Ochang 28119, Cheongju, South Korea; [Huh, Yang Hoon] Korea Basic Sci Inst, Ctr Electron Microscopy Res, Ochang 28119, Cheongju, South Korea; [Kwon, Yong Tae] Seoul Natl Univ, Coll Med, Dept Biomed Sci, Prot Metab Med Res Ctr, Seoul 03080, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 NATURE PUBLISHING GROUP
- 발행년도 2019
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000172005
- 본문언어 영어
- Published As https://dx.doi.org/10.1038/s41419-019-1778-8
초록/요약
The initiation of centrosome duplication is regulated by the Plk4/STIL/hsSAS-6 axis; however, the involvement of other centrosomal proteins in this process remains unclear. In this study, we demonstrate that Cep131 physically interacts with Plk4 following phosphorylation of residues S21 and T205. Localizing at the centriole, phosphorylated Cep131 has an increased capability to interact with STIL, leading to further activation and stabilization of Plk4 for initiating centrosome duplication. Moreover, we found that Cep131 overexpression resulted in centrosome amplification by excessive recruitment of STIL to the centriole and subsequent stabilization of Plk4, contributing to centrosome amplification. The xenograft mouse model also showed that both centrosome amplification and colon cancer growth were significantly increased by Cep131 overexpression. These findings demonstrate that Cep131 is a novel substrate of Plk4, and that phosphorylation or dysregulated Cep131 overexpression promotes Plk4 stabilization and therefore centrosome amplification, establishing a perspective in understanding a relationship between centrosome amplification and cancer development.
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