Aurora-A interacts with Cyclin B1 and enhances its stability

Qin, Lili; Tong, Tong; Song, Yongmei; Xue, Liyan; Fan, Feiyue; Zhan, Qimin

doi:10.1016/j.canlet.2008.10.011

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Volume 275, Issue 1 , Pages 77-85, 8 March 2009

Aurora-A interacts with Cyclin B1 and enhances its stability

Lili Qin
- State Key Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
- Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China
Tong Tong
- State Key Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
Yongmei Song
- State Key Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
Liyan Xue
- State Key Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
Feiyue Fan
- Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China
Qimin Zhan
- State Key Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
- Corresponding author. Tel.: +86 10 87788422; fax: +86 10 67715058.

Received 14 February 2008; received in revised form 25 September 2008; accepted 2 October 2008. published online 25 November 2008.

Abstract

The mitotic regulator Aurora-A is an oncogenic protein that is over-expressed in many types of human tumors. However, the underlying mechanism through which Aurora-A promotes tumorigenesis remains unclear. Here, we show that overexpression of Aurora-A causes an elevation of Cyclin B1 expression. Cyclin B1 degradation is delayed in Aurora-A over-expressing cells, which depends on Aurora-A kinase activity. In contrast, Aurora-A RNAi enhances Cyclin B1 degradation. Furthermore, we found that Aurora-A interacts with Cyclin B1, and that Aurora-A overexpression reduces the interaction of Cyclin B1 with APC subunits. In human esophageal squamous cell carcinomas (ESCC), overexpression of Aurora-A was correlated with deregulated expression of Cyclin B1. Taken together, these findings suggest that overexpression of Aurora-A may stabilize Cyclin B1 through inhibiting its degradation. These results provide new insight into the mechanism of how deregulated Aurora-A contributes to genomic instability and carcinogenesis.

Keywords: Cyclin B1, Aurora-A, Cell cycle, Protein stability, Carcinogenesis