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Title 

Cep131 overexpression promotes centrosome amplification and colon cancer progression by regulating Plk4 stability

Authors 

Dong Hyun KimJong Seog AhnHo Jin HanHye-Min KimJoonsung HwangKyung Ho LeeHyunjoo ChaIn Ja RyooJae-Hyuk JangSung-Kyun KoJin Ok YangHee Gu LeeSangku LeeE J SongJ Y KimY H HuhY T KwonNak Kyun SoungBo Yeon Kim

Publisher 

Springer Nature

Issue Date 

2019

Citation 

Cell Death and Disease

Abstract 

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.

URI 

https://doi.org/10.1038/s41419-019-1778-8

ISSN 

2041-4889

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-10-29


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