title: Overexpression of Aurora-C interferes with the spindle checkpoint by promoting the degradation of Aurora-B.
abstract: The chromosomal passenger complex (CPC) plays a pivotal role in controlling accurate chromosome segregation and cytokinesis during cell division. Aurora-B, one of the chromosomal passenger proteins, is important for the mitotic spindle assembly checkpoint (SAC). Previous reports noted that Aurora-C is predominantly expressed in male germ cells and has the same subcellular localization as Aurora-B. Increasing evidence indicates that Aurora-C is overexpressed in many somatic cancers, although its function is uncertain. Our previous study showed that the aberrant expression of Aurora-C increases the tumorigenicity of cancer cells. Here, we demonstrate that overexpressed Aurora-C displaces the centromeric localization of CPCs, including INCENP, survivin, and Aurora-B. When cells were treated with nocodazole to turn on SAC, both the Aurora-B protein stability and kinase activity were affected by overexpressed Aurora-C. As a result, the activation of spindle checkpoint protein, BubR1, and phosphorylation of histone H3 and MCAK were also eliminated in Aurora-C-overexpressing cells. Thus, our results suggest that aberrantly expressed Aurora-C in somatic cancer cells may impair SAC by displacing the centromeric localization of CPCs.
authors.affiliation: Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: B-W
authors.initials: BW
authors.lastname: Lin
authors.affiliation: Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Y-C
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: P-Y
authors.initials: PY
authors.lastname: Chang-Liao
authors.affiliation: Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Lin
authors.affiliation: Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: S-T
authors.initials: ST
authors.lastname: Yang
authors.affiliation: Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: J-H
authors.initials: JH
authors.lastname: Tsou
authors.affiliation: Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: K-C
authors.initials: KC
authors.lastname: Chang
authors.affiliation: Department of Pathology, Kuo General Hospital, Tainan, Taiwan.
authors.forename: Y-W
authors.initials: YW
authors.lastname: Liu
authors.affiliation: Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: J T
authors.initials: JT
authors.lastname: Tseng
authors.affiliation: Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: C-T
authors.initials: CT
authors.lastname: Lee
authors.affiliation: Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: J-C
authors.initials: JC
authors.lastname: Lee
authors.affiliation: 1] Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan [2] Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan [3] Infectious Disease and Signaling Research Center, National Cheng Kung University, Tainan, Taiwan [4] Institute for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: L-Y
authors.initials: LY
authors.lastname: Hung
mesh_terms: D064107:Aurora Kinase B / Q000378:metabolism*; D064108:Aurora Kinase C / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D002503:Centromere / Q000201:enzymology; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D016547:Kinesins / Q000378:metabolism; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D009361:Neoplasm Invasiveness; D015739:Nocodazole / Q000494:pharmacology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D059748:Proteolysis; D008941:Spindle Apparatus / Q000187:drug effects / Q000201:enzymology*; D000077022:Survivin; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation
chemical_list: C107489:BIRC5 protein, human; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; C083767:INCENP protein, human; D051034:Inhibitor of Apoptosis Proteins; C091489:KIF2C protein, human; D000077022:Survivin; C576921:AURKB protein, human; C576927:AURKC protein, human; D064107:Aurora Kinase B; D064108:Aurora Kinase C; C584277:BUB1 protein, human; D017346:Protein Serine-Threonine Kinases; D016547:Kinesins; D015739:Nocodazole