title: Oxidative stress induces mitotic arrest by inhibiting Aurora A-involved mitotic spindle formation.
abstract: Oxidative stress contributes to the oxidative modification of cellular components, including lipids, proteins and DNA, and results in DNA damage, cell cycle arrest, cellular dysfunction and apoptosis. However, the mechanism underlying oxidative stress-induced mitotic abnormalities is not fully understood. In this study, we demonstrated that exogenous and endogenous reactive oxygen species (ROS) promoted mitotic arrest. Delayed formation and abnormal function of the mitotic spindle, which directly impeded mitosis and promoted abnormal chromosome separation, was responsible for ROS-induced mitotic arrest. As a key regulator of mitotic spindle assembly, Aurora A kinase was hyperphosphorylated in early mitosis under oxidative stress, which may disturb the function of Aurora A in mitotic spindle formation. Our findings identified a mechanism by which ROS regulate mitotic progression and indicated a potential molecular target for the treatment of oxidative stress-related diseases.
authors.affiliation: Key Laboratory of Cell Proliferation and Regulation Biology, College of Life Sciences, Beijing Normal University, 19 Xinjiekouwai Avenue, Beijing 100875, China.
authors.forename: Guang-Fei
authors.initials: GF
authors.lastname: Wang
authors.affiliation: Beijing Institute of Biotechnology, 27 Taiping Rd, Haidian District, Beijing 100850, China.
authors.forename: Qincai
authors.initials: Q
authors.lastname: Dong
authors.affiliation: Beijing Institute of Biotechnology, 27 Taiping Rd, Haidian District, Beijing 100850, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Beijing Institute of Disease Control and Prevention, Beijing 100071, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Beijing Institute of Biotechnology, 27 Taiping Rd, Haidian District, Beijing 100850, China.
authors.forename: Quanbin
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Beijing Institute of Biotechnology, 27 Taiping Rd, Haidian District, Beijing 100850, China. Electronic address: cao_c@sohu.com.
authors.forename: Cheng
authors.initials: C
authors.lastname: Cao
authors.affiliation: Beijing Institute of Biotechnology, 27 Taiping Rd, Haidian District, Beijing 100850, China. Electronic address: liux931932@163.com.
authors.forename: Xuan
authors.initials: X
authors.lastname: Liu
mesh_terms: D017209:Apoptosis; D064096:Aurora Kinase A / Q000378:metabolism*; D059447:Cell Cycle Checkpoints; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D061986:MCF-7 Cells; D008938:Mitosis; D018384:Oxidative Stress; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D008941:Spindle Apparatus / Q000378:metabolism*; D024483:Vitamin K 3 / Q000494:pharmacology
chemical_list: D024483:Vitamin K 3; D006861:Hydrogen Peroxide; C576917:AURKA protein, human; D064096:Aurora Kinase A
keywords: Aurora A; Mitotic arrest; Phosphorylation; ROS; Spindle