Aurora-A interacts with Cyclin B1 and enhances its stability.
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.
Qin
Lili
L
State Key Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Tong
Tong
T
Song
Yongmei
Y
Xue
Liyan
L
Fan
Feiyue
F
Zhan
Qimin
Q
D064127:Aurora Kinases; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000737:chemistry; D045744:Cell Line, Tumor; D019926:Cyclin B / Q000378:metabolism*; D056744:Cyclin B1; D004938:Esophageal Neoplasms / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology*; D034622:RNA Interference; D025801:Ubiquitin / Q000737:chemistry
C534699:CCNB1 protein, human; D018797:Cell Cycle Proteins; D019926:Cyclin B; D056744:Cyclin B1; D025801:Ubiquitin; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases