Abstract
Aurora kinases are emerging as key regulators of centrosome function, chromosome segregation and cytokinesis. We previously isolated Aurora-C (Aie1), a third type of Aurora kinase, in a screen for kinases expressed in mouse sperm and eggs. Currently, we know very little about the precise localization and function of Aurora-C. Immunofluorescence analysis of ectopically expressed GFP-Aurora-C has revealed that Aurora-C is a new member of the chromosomal passenger proteins localizing first to the centromeres and then to the central spindles during cytokinesis. In order to study the potential role of Aurora-C, we examined the effects of a kinase-deficient (KD) mutant (AurC-KD) in HeLa Tet-Off cells under tetracycline control. Our results showed that overexpression of AurC-KD causes defects in cell division and induces polyploidy and apoptosis. Interestingly, AurC-KD overexpression also inhibits centromere/kinetochore localization of Aurora-B, Bub1, and BubR1, reduces histone H3 phosphorylation, and disrupts the association of INCENP with Aurora-B. Together, our results showed that Aurora-C is a chromosomal passenger protein, which may serve as a key regulator in cell division.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis
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Aurora Kinase B
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Aurora Kinase C
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Aurora Kinases
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Cell Cycle Proteins
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Cell Division
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Cell Proliferation
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Cell Separation
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Centromere / metabolism
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Centrosome / ultrastructure
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Chromosomal Proteins, Non-Histone / metabolism*
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Cytokinesis
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DNA, Complementary / metabolism
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Flow Cytometry
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Green Fluorescent Proteins / metabolism
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HeLa Cells
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Histones / metabolism
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Humans
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Immunoblotting
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In Situ Nick-End Labeling
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Macromolecular Substances
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Microscopy, Fluorescence
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Mutagenesis
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Mutation
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Phosphorylation
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Polyploidy
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Protein Binding
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Protein Kinases
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Protein Serine-Threonine Kinases / genetics*
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Protein Serine-Threonine Kinases / metabolism*
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Protein Serine-Threonine Kinases / physiology*
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Spindle Apparatus
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Tetracycline / pharmacology
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Time Factors
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Transfection
Substances
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Bub1b protein, mouse
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Cell Cycle Proteins
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Chromosomal Proteins, Non-Histone
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DNA, Complementary
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Histones
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INCENP protein, human
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Incenp protein, mouse
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Macromolecular Substances
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Green Fluorescent Proteins
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Protein Kinases
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AURKB protein, human
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AURKC protein, human
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Aurkb protein, mouse
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Aurkc protein, mouse
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Aurora Kinase B
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Aurora Kinase C
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Aurora Kinases
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BUB1 protein, human
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Bub1 protein, mouse
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Bub1 spindle checkpoint protein
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Protein Serine-Threonine Kinases
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Tetracycline