Viral-Mediated AURKB Cleavage Promotes Cell Segregation and Tumorigenesis
Summary: 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...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2019-03-01
|
Series: | Cell Reports |
Online Access: | http://www.sciencedirect.com/science/article/pii/S221112471930292X |
id |
doaj-2116da1b70cd448f9e6e578f7dc5bb55 |
---|---|
record_format |
Article |
spelling |
doaj-2116da1b70cd448f9e6e578f7dc5bb552020-11-25T01:30:56ZengElsevierCell Reports2211-12472019-03-01261336573671.e5Viral-Mediated AURKB Cleavage Promotes Cell Segregation and TumorigenesisQing Zhu0Ling Ding1Zhenguo Zi2Shujun Gao3Chong Wang4Yuyan Wang5Caixia Zhu6Zhenghong Yuan7Fang Wei8Qiliang Cai9MOE and MOH Key Laboratory of Medical Molecular Virology, School of Basic Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaMOE and MOH Key Laboratory of Medical Molecular Virology, School of Basic Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaShengYushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, ChinaHospital and Institute of Obstetrics and Gynecology, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaMOE and MOH Key Laboratory of Medical Molecular Virology, School of Basic Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaMOE and MOH Key Laboratory of Medical Molecular Virology, School of Basic Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaMOE and MOH Key Laboratory of Medical Molecular Virology, School of Basic Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaMOE and MOH Key Laboratory of Medical Molecular Virology, School of Basic Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaShengYushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, ChinaMOE and MOH Key Laboratory of Medical Molecular Virology, School of Basic Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, China; Expert Workstation, Baoji Central Hospital, Baoji, 721008 Shaanxi Province, China; Corresponding authorSummary: 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 et al. find that proteolytic cleavage of AURKB occurs in several oncovirus-associated cancer cells. Specifically, the oncovirus antigen LANA cleaves AURKB to promote the metaphase-to-telophase transition, thereby inducing host cell segregation and tumorigenesis. Keywords: AURKB, protein cleavage, KSHV, HPV, EBV, oncovirus, cell segregation, tumorigenesishttp://www.sciencedirect.com/science/article/pii/S221112471930292X |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Qing Zhu Ling Ding Zhenguo Zi Shujun Gao Chong Wang Yuyan Wang Caixia Zhu Zhenghong Yuan Fang Wei Qiliang Cai |
spellingShingle |
Qing Zhu Ling Ding Zhenguo Zi Shujun Gao Chong Wang Yuyan Wang Caixia Zhu Zhenghong Yuan Fang Wei Qiliang Cai Viral-Mediated AURKB Cleavage Promotes Cell Segregation and Tumorigenesis Cell Reports |
author_facet |
Qing Zhu Ling Ding Zhenguo Zi Shujun Gao Chong Wang Yuyan Wang Caixia Zhu Zhenghong Yuan Fang Wei Qiliang Cai |
author_sort |
Qing Zhu |
title |
Viral-Mediated AURKB Cleavage Promotes Cell Segregation and Tumorigenesis |
title_short |
Viral-Mediated AURKB Cleavage Promotes Cell Segregation and Tumorigenesis |
title_full |
Viral-Mediated AURKB Cleavage Promotes Cell Segregation and Tumorigenesis |
title_fullStr |
Viral-Mediated AURKB Cleavage Promotes Cell Segregation and Tumorigenesis |
title_full_unstemmed |
Viral-Mediated AURKB Cleavage Promotes Cell Segregation and Tumorigenesis |
title_sort |
viral-mediated aurkb cleavage promotes cell segregation and tumorigenesis |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2019-03-01 |
description |
Summary: 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 et al. find that proteolytic cleavage of AURKB occurs in several oncovirus-associated cancer cells. Specifically, the oncovirus antigen LANA cleaves AURKB to promote the metaphase-to-telophase transition, thereby inducing host cell segregation and tumorigenesis. Keywords: AURKB, protein cleavage, KSHV, HPV, EBV, oncovirus, cell segregation, tumorigenesis |
url |
http://www.sciencedirect.com/science/article/pii/S221112471930292X |
work_keys_str_mv |
AT qingzhu viralmediatedaurkbcleavagepromotescellsegregationandtumorigenesis AT lingding viralmediatedaurkbcleavagepromotescellsegregationandtumorigenesis AT zhenguozi viralmediatedaurkbcleavagepromotescellsegregationandtumorigenesis AT shujungao viralmediatedaurkbcleavagepromotescellsegregationandtumorigenesis AT chongwang viralmediatedaurkbcleavagepromotescellsegregationandtumorigenesis AT yuyanwang viralmediatedaurkbcleavagepromotescellsegregationandtumorigenesis AT caixiazhu viralmediatedaurkbcleavagepromotescellsegregationandtumorigenesis AT zhenghongyuan viralmediatedaurkbcleavagepromotescellsegregationandtumorigenesis AT fangwei viralmediatedaurkbcleavagepromotescellsegregationandtumorigenesis AT qiliangcai viralmediatedaurkbcleavagepromotescellsegregationandtumorigenesis |
_version_ |
1725088861125607424 |