Viral-Mediated AURKB Cleavage Promotes Cell Segregation and Tumorigenesis

摘要

Aurora kinase B (AURKB), a central regulator of chromosomesegregation and cytokinesis, is aberrantlyexpressed in various cancer cells. However, the relationshipof AURKB and oncogenic viruses in cancerprogression remains unclear. Here, we reveal thatN-cleaved isoforms of AURKB exist in several oncovirus-associatedtumor cells and patient cancertissues, including Kaposi’s sarcoma-associatedherpesvirus (KSHV), Epstein-Barr virus (EBV), and humanpapillomavirus virus (HPV). Mechanistically, inKSHV-infected tumor cells, the latent viral antigenLANA cleaves AURKB at Asp76 in a serine proteasedependentmanner. The N0-AURKB relocalizes tothe spindle pole and promotes the metaphase-totelophasetransition in mitotic cells. Introduction ofN0-AURKB but not C0-AURKB promotes colony formationand malignant growth of tumor cells in vitroand in vivo using a murine xenograft model. Altogether,our findings uncover a proteolytic cleavagemechanism by which oncoviruses induce cancercell segregation and tumorigenesis.