Exploring the functional interactions between Aurora B, INCENP, and survivin in mitosis

The function of the Aurora B kinase at centromeres and the central spindle is crucial for chromosome segregation and cytokinesis, respectively. Herein, we have investigated the regulation of human Aurora B by its complex partners inner centromere protein (INCENP) and survivin. We found that overexpr...

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Bibliographic Details
Published in:Molecular biology of the cell 2003-08, Vol.14 (8), p.3325-3341
Main Authors: Honda, Reiko, Körner, Roman, Nigg, Erich A
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Aurora Kinase B
Aurora Kinases
Cell Division
Cells, Cultured
Centromere - metabolism
Chromosomal Proteins, Non-Histone - metabolism
Cloning, Molecular
Enzyme Activation
HeLa Cells
Humans
Inhibitor of Apoptosis Proteins
Microtubule-Associated Proteins - metabolism
Mitosis
Mutation
Neoplasm Proteins
Phosphorylation
Protein-Serine-Threonine Kinases - metabolism
RNA Interference
Spindle Apparatus - metabolism
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Summary:The function of the Aurora B kinase at centromeres and the central spindle is crucial for chromosome segregation and cytokinesis, respectively. Herein, we have investigated the regulation of human Aurora B by its complex partners inner centromere protein (INCENP) and survivin. We found that overexpression of a catalytically inactive, dominant-negative mutant of Aurora B impaired the localization of the entire Aurora B/INCENP/survivin complex to centromeres and the central spindle and severely disturbed mitotic progression. Similar results were also observed after depletion, by RNA interference, of either Aurora B, INCENP, or survivin. These data suggest that Aurora B kinase activity and the formation of the Aurora B/INCENP/survivin complex both contribute to its proper localization. Using recombinant proteins, we found that Aurora B kinase activity was stimulated by INCENP and that the C-terminal region of INCENP was sufficient for activation. Under identical assay conditions, survivin did not detectably influence kinase activity. Human INCENP was a substrate of Aurora B and mass spectrometry identified three consecutive residues (threonine 893, serine 894, and serine 895) containing at least two phosphorylation sites. A nonphosphorylatable mutant (TSS893-895AAA) was a poor activator of Aurora B, demonstrating that INCENP phosphorylation is important for kinase activation.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.E02-11-0769