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

Dong Hyun Kim, Jong Seog Ahn, Ho Jin Han, Hye Min Kim, Joonsung Hwang, Kyung Ho Lee, Hyunjoo Cha-Molstad, In Ja Ryoo, Jae Hyuk Jang, Sung Kyun Ko, Jin Ok Yang, Hee Gu Lee, Sangku Lee, Eun Joo Song, Jin Young Kim, Yang Hoon Huh, Yong Tae Kwon, Nak Kyun Soung, Bo Yeon Kim

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number570
JournalCell Death and Disease
Volume10
Issue number8
DOIs
StatePublished - 1 Aug 2019

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    Kim, D. H., Ahn, J. S., Han, H. J., Kim, H. M., Hwang, J., Lee, K. H., Cha-Molstad, H., Ryoo, I. J., Jang, J. H., Ko, S. K., Yang, J. O., Lee, H. G., Lee, S., Song, E. J., Kim, J. Y., Huh, Y. H., Kwon, Y. T., Soung, N. K., & Kim, B. Y. (2019). Cep131 overexpression promotes centrosome amplification and colon cancer progression by regulating Plk4 stability. Cell Death and Disease, 10(8), [570]. https://doi.org/10.1038/s41419-019-1778-8