title: Acetylation of Aurora B by TIP60 ensures accurate chromosomal segregation.
abstract: Faithful segregation of chromosomes in mammalian cells requires bi-orientation of sister chromatids, which relies on the sensing of correct attachments between spindle microtubules and kinetochores. Although the mechanisms underlying cyclin-dependent kinase 1 (CDK1) activation, which triggers mitotic entry, have been extensively studied, the regulatory mechanisms that couple CDK1-cyclin B activity to chromosome stability are not well understood. Here, we identified a signaling axis in which Aurora B activity is modulated by CDK1-cyclin B via the acetyltransferase TIP60 in human cell division. CDK1-cyclin B phosphorylates Ser90 of TIP60, which elicits TIP60-dependent acetylation of Aurora B and promotes accurate chromosome segregation in mitosis. Mechanistically, TIP60 acetylation of Aurora B at Lys215 protects Aurora B's activation loop from dephosphorylation by the phosphatase PP2A to ensure a robust, error-free metaphase-anaphase transition. These findings delineate a conserved signaling cascade that integrates protein phosphorylation and acetylation with cell cycle progression for maintenance of genomic stability.
authors.affiliation: Anhui Key Laboratory for Cellular Dynamics &Chemical Biology, Hefei, China.|Laboratory for Organelle Dynamics &Plasticity Control, University of Science &Technology of China School of Life Sciences, Hefei, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Mo
authors.affiliation: Anhui Key Laboratory for Cellular Dynamics &Chemical Biology, Hefei, China.|Laboratory for Organelle Dynamics &Plasticity Control, University of Science &Technology of China School of Life Sciences, Hefei, China.
authors.forename: Xiaoxuan
authors.initials: X
authors.lastname: Zhuang
authors.affiliation: Anhui Key Laboratory for Cellular Dynamics &Chemical Biology, Hefei, China.|Laboratory for Organelle Dynamics &Plasticity Control, University of Science &Technology of China School of Life Sciences, Hefei, China.|Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Hefei, China.|Hefei National Laboratory for Physical Sciences at Nanoscale, Hefei, China.|Molecular Imaging Center, Morehouse School of Medicine, Atlanta, Georgia, USA.
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Molecular Imaging Center, Morehouse School of Medicine, Atlanta, Georgia, USA.
authors.forename: Phil Y
authors.initials: PY
authors.lastname: Yao
authors.affiliation: Anhui Key Laboratory for Cellular Dynamics &Chemical Biology, Hefei, China.|Laboratory for Organelle Dynamics &Plasticity Control, University of Science &Technology of China School of Life Sciences, Hefei, China.|Molecular Imaging Center, Morehouse School of Medicine, Atlanta, Georgia, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Qin
authors.affiliation: Molecular Imaging Center, Morehouse School of Medicine, Atlanta, Georgia, USA.|Department of Medical Cell Biology, Beijing University of Chinese Medicine, Beijing, China.
authors.forename: Zeqi
authors.initials: Z
authors.lastname: Su
authors.affiliation: Anhui Key Laboratory for Cellular Dynamics &Chemical Biology, Hefei, China.|Laboratory for Organelle Dynamics &Plasticity Control, University of Science &Technology of China School of Life Sciences, Hefei, China.|Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Hefei, China.|Hefei National Laboratory for Physical Sciences at Nanoscale, Hefei, China.
authors.forename: Jianye
authors.initials: J
authors.lastname: Zang
authors.affiliation: Anhui Key Laboratory for Cellular Dynamics &Chemical Biology, Hefei, China.|Laboratory for Organelle Dynamics &Plasticity Control, University of Science &Technology of China School of Life Sciences, Hefei, China.|Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Hefei, China.|Hefei National Laboratory for Physical Sciences at Nanoscale, Hefei, China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Anhui Key Laboratory for Cellular Dynamics &Chemical Biology, Hefei, China.|Laboratory for Organelle Dynamics &Plasticity Control, University of Science &Technology of China School of Life Sciences, Hefei, China.|State Key Laboratory of Respiratory Diseases, Guangzhou, China.
authors.forename: Jiancun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Anhui Key Laboratory for Cellular Dynamics &Chemical Biology, Hefei, China.|Laboratory for Organelle Dynamics &Plasticity Control, University of Science &Technology of China School of Life Sciences, Hefei, China.|Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Hefei, China.|Hefei National Laboratory for Physical Sciences at Nanoscale, Hefei, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Dou
authors.affiliation: Anhui Key Laboratory for Cellular Dynamics &Chemical Biology, Hefei, China.|Laboratory for Organelle Dynamics &Plasticity Control, University of Science &Technology of China School of Life Sciences, Hefei, China.|Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Hefei, China.|Hefei National Laboratory for Physical Sciences at Nanoscale, Hefei, China.
authors.forename: Changlin
authors.initials: C
authors.lastname: Tian
authors.affiliation: Anhui Key Laboratory for Cellular Dynamics &Chemical Biology, Hefei, China.|Laboratory for Organelle Dynamics &Plasticity Control, University of Science &Technology of China School of Life Sciences, Hefei, China.|Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Hefei, China.|Hefei National Laboratory for Physical Sciences at Nanoscale, Hefei, China.
authors.forename: Maikun
authors.initials: M
authors.lastname: Teng
authors.affiliation: Anhui Key Laboratory for Cellular Dynamics &Chemical Biology, Hefei, China.|Laboratory for Organelle Dynamics &Plasticity Control, University of Science &Technology of China School of Life Sciences, Hefei, China.|Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Hefei, China.|Hefei National Laboratory for Physical Sciences at Nanoscale, Hefei, China.
authors.forename: Liwen
authors.initials: L
authors.lastname: Niu
authors.affiliation: Comprehensive Cancer Center, University of Alabama, Birmingham, Alabama, USA.
authors.forename: Donald L
authors.initials: DL
authors.lastname: Hill
authors.affiliation: Anhui Key Laboratory for Cellular Dynamics &Chemical Biology, Hefei, China.|Laboratory for Organelle Dynamics &Plasticity Control, University of Science &Technology of China School of Life Sciences, Hefei, China.
authors.forename: Guowei
authors.initials: G
authors.lastname: Fang
authors.affiliation: Molecular Imaging Center, Morehouse School of Medicine, Atlanta, Georgia, USA.|Department of Medical Cell Biology, Beijing University of Chinese Medicine, Beijing, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Ding
authors.affiliation: Anhui Key Laboratory for Cellular Dynamics &Chemical Biology, Hefei, China.|Laboratory for Organelle Dynamics &Plasticity Control, University of Science &Technology of China School of Life Sciences, Hefei, China.|Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Hefei, China.|Hefei National Laboratory for Physical Sciences at Nanoscale, Hefei, China.
authors.forename: Chuanhai
authors.initials: C
authors.lastname: Fu
authors.affiliation: Anhui Key Laboratory for Cellular Dynamics &Chemical Biology, Hefei, China.|Laboratory for Organelle Dynamics &Plasticity Control, University of Science &Technology of China School of Life Sciences, Hefei, China.|Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Hefei, China.|Hefei National Laboratory for Physical Sciences at Nanoscale, Hefei, China.
authors.forename: Xuebiao
authors.initials: X
authors.lastname: Yao
mesh_terms: D000107:Acetylation; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D064107:Aurora Kinase B / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation / Q000235:genetics / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D057809:HEK293 Cells; D006367:HeLa Cells; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D018386:Kinetochores / Q000201:enzymology* / Q000648:ultrastructure; D000074443:Lysine Acetyltransferase 5; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D010957:Plasmids; D059008:Time-Lapse Imaging
chemical_list: D000911:Antibodies, Monoclonal; D004791:Enzyme Inhibitors; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5; C576921:AURKB protein, human; D064107:Aurora Kinase B
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