Cep131 overexpression promotes centrosome amplification and colon cancer progression by regulating Plk4 stability
| Autor: | Hye-Min Kim, Jong Seog Ahn, In Ja Ryoo, Yang Hoon Huh, Sangku Lee, Jae-Hyuk Jang, Jinyoung Kim, Yong Tae Kwon, Bo Yeon Kim, Nak Kyun Soung, Jin Ok Yang, Eun Joo Song, Kyung Ho Lee, Dong Hyun Kim, Joonsung Hwang, Ho Jin Han, Sung Kyun Ko, Hee Gu Lee, Hyunjoo Cha-Molstad |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
PLK4
Cancer Research Centriole Cell division Colorectal cancer Immunology Cell Cycle Proteins Biology Protein Serine-Threonine Kinases Article 03 medical and health sciences Cellular and Molecular Neuroscience Mice 0302 clinical medicine Cell Line Tumor medicine Animals Humans Centrosome duplication Phosphorylation lcsh:QH573-671 030304 developmental biology Centrosome 0303 health sciences lcsh:Cytology Intracellular Signaling Peptides and Proteins Cell Biology Oncogenes medicine.disease HCT116 Cells Cell biology Gene Expression Regulation Neoplastic Cytoskeletal Proteins HEK293 Cells 030220 oncology & carcinogenesis Colonic Neoplasms Disease Progression Heterografts Cancer development |
| Zdroj: | Cell Death and Disease, Vol 10, Iss 8, Pp 1-16 (2019) Cell Death & Disease |
| ISSN: | 2041-4889 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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