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Aurora-B phosphorylation in vitro identifies a residue of survivin that is essential for its localization and binding to inner centromere protein (INCENP) in vivo.
journal contribution
posted on 2023-06-08, 01:00 authored by Sally P Wheatley, Alexander J Henzing, Helen Dodson, Walid Khaled, William C EarnshawThe chromosomal passengers aurora-B kinase, INCENP and survivin, are essential proteins that have been implicated in the regulation of metaphase chromosome alignment, spindle checkpoint function and cytokinesis. All three share a common pattern of localization and it was recently demonstrated that aurora-B, INCENP and survivin are present in a complex in Xenopus eggs and S.cerevisiae. The presence of aurora-B kinase in the complex, and its ability to bind the other components directly, suggests that INCENP and survivin could potentially be aurora-B substrates. This hypothesis was recently proven for INCENP in vitro. Here we report that human survivin is specifically phosphorylated in vitro by aurora-B kinase at threonine117 in its carboxyl alpha-helical coil. Mutation of threonine117 to alanine prevents survivin phosphorylation by aurora-B in vitro, but does not alter its localization in HeLa cells. By contrast, a phospho-mimic, in which threonine117 was mutated to glutamic acid, was unable to localize correctly at any stage in mitosis. Mutation at threonine 117 also prevented immunoprecipitation of INCENP with survivin in vivo. These data suggest that phosphorylation of survivin at threonine117 by aurora-B may regulate targeting of survivin, and possibly the entire passenger complex, in mammals.
History
Publication status
- Published
Journal
Journal of Biological ChemistryISSN
0021-9258External DOI
Issue
7Volume
279Page range
5655-5660Pages
6.0Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Notes
SPW directed the research and was corresponding author. First demonstration that human survivin is phosphorylated by aurora-B kinase, mapping of the site, and demonstration that a putative phosphomimic cannot localise correctly during mitosis.Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2012-02-06Usage metrics
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