Overexpression of an Aurora-C kinase-deficient mutant disrupts the Aurora-B/INCENP complex and induces polyploidy.
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.
Chen
Hua-Ling
HL
Institute of Biomedical Sciences, Academia Sinica, 128, Academia Road, Sec. 2, Taipei, 11529, Taiwan, ROC.
Tang
Chieh-Ju C
CJ
Chen
Chiung-Ya
CY
Tang
Tang K
TK
D017209:Apoptosis; D064107:Aurora Kinase B; D064108:Aurora Kinase C; D064127:Aurora Kinases; D018797:Cell Cycle Proteins; D002455:Cell Division; D049109:Cell Proliferation; D002469:Cell Separation; D002503:Centromere / Q000378:metabolism; D018385:Centrosome / Q000648:ultrastructure; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D048749:Cytokinesis; D018076:DNA, Complementary / Q000378:metabolism; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D020287:In Situ Nick-End Labeling; D046911:Macromolecular Substances; D008856:Microscopy, Fluorescence; D016296:Mutagenesis; D009154:Mutation; D010766:Phosphorylation; D011123:Polyploidy; D011485:Protein Binding; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology*; D008941:Spindle Apparatus; D013752:Tetracycline / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection
C584278:Bub1b protein, mouse; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D018076:DNA, Complementary; D006657:Histones; C083767:INCENP protein, human; C513185:Incenp protein, mouse; D046911:Macromolecular Substances; D049452:Green Fluorescent Proteins; D011494:Protein Kinases; C576921:AURKB protein, human; C576927:AURKC protein, human; C576924:Aurkb protein, mouse; C576928:Aurkc protein, mouse; D064107:Aurora Kinase B; D064108:Aurora Kinase C; D064127:Aurora Kinases; C584277:BUB1 protein, human; C584281:Bub1 protein, mouse; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases; D013752:Tetracycline