A Study of Viral-Mediated AURKB Cleavage Promotes Cell Segregation and Tumorigenesis. Zhu Q et al

Published: 25 March 2019| Version 1 | DOI: 10.17632/s5d8fkzwhj.1
Qing Zhu, Ling Ding, Zhenguo Zi, Shujun Gao, Chong Wang, Yuyan Wang, Caixia Zhu, Zhenghong Yuan, Fang Wei, Qiliang Cai


Aurora B (AURKB) kinase, a central regulator of chromosome segregation and cytokinesis, is aberrantly expressed in various cancer cells. However, the relationship of AURKB and oncogenic viruses in cancer progression remains unclear. Here, we reveal that N-cleaved isoforms of AURKB exist in several oncovirus-associated tumor cells and patient cancer tissues, including Kaposi’s sarcoma herpesvirus (KSHV), Epstein-Barr virus (EBV), and human papillomavirus virus (HPV). Mechanistically, in KSHV-infected tumor cells,the latent viral antigen LANA cleaves AURKB Asp76 in a serine protease-dependent manner. The N’-cleaved AURKB relocalizes to the spindle pole and promotes the metaphase-to-telophase transition in mitotic cells. Introduction of N’-AURKB but not C’-AURKB promotes colony formation and malignant growth of tumor cells in vitro and in vivo using a murine xenograft model. Altogether, our findings uncover a proteolytic cleavage mechanism by which oncoviruses induce cancer cell segregation and tumorigenesis.