Viral-Mediated AURKB Cleavage Promotes Cell Segregation and Tumorigenesis.
Aurora kinase B (AURKB), 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-associated herpesvirus (KSHV), Epstein-Barr virus (EBV), and human papillomavirus virus (HPV). Mechanistically, in KSHV-infected tumor cells, the latent viral antigen LANA cleaves AURKB at Asp76 in a serine protease-dependent manner. The N'-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.
['Zhu|Qing|Q|', 'Ding|Ling|L|', 'Zi|Zhenguo|Z|', 'Gao|Shujun|S|', 'Wang|Chong|C|', 'Wang|Yuyan|Y|', 'Zhu|Caixia|C|', 'Yuan|Zhenghong|Z|', 'Wei|Fang|F|', 'Cai|Qiliang|Q|']
D000328:Adult D000368:Aged D000818:Animals D064107:Aurora Kinase B D063646:Carcinogenesis D020090:Chromosome Segregation D005260:Female D057809:HEK293 Cells D006367:HeLa Cells D019288:Herpesvirus 8, Human D006801:Humans D008297:Male D051379:Mice D016688:Mice, Inbred NOD D008875:Middle Aged D008938:Mitosis D009369:Neoplasms D009858:Oncogenic Viruses D023041:Xenograft Model Antitumor Assays D055815:Young Adult
AURKB cell segregation tumorigenesis KSHV EBV HPV oncovirus protein cleavage