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Phosphorylation by aurora-B negatively regulates survivin function during mitosis
journal contribution
posted on 2023-06-08, 00:15 authored by Sally P Wheatley, Rachel M Barrett, Paul D Andrews, Rene H Medema, Simon Morley, Jason R Swedlow, Susanne M A LensSurvivin operates in a complex with aurora B kinase and is phosphorylated by it on threonine 117 in vitro. Here we ask whether phosphorylation of survivin by aurora B kinase regulates its function during mitosis in vivo. Using a phospho-specific antibody we first establish that survivin is phosphorylated at T117 during mitosis and is present at the midbody during cytokinesis. Next we use two independent RNAi complementation approaches to investigate threonine 117 mutants in survivin depleted cells. Our data suggest that while non-phosphorylatable survivin, survivinT117A, can substitute for the wild type protein, a phosphomimic, survivinT117E cannot restore viability, nor can it complement chromosome congression and spindle checkpoint defects that arise due to depletion of endogenous survivin. Fluorescence imaging and fluorescence recovery after photobleaching analysis suggest that the phosphomimic has reduced affinity for centromeres compared with the non-phosphorylatable form. We conclude that survivin is phosphorylated at T117 during mitosis, and once phosphorylated, dephosphorylation is crucial for chromosome congression and progression into anaphase.
History
Publication status
- Published
Journal
Cell CycleISSN
1538-4101External DOI
Issue
10Volume
6Page range
1220-1230Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Notes
SPW executed and/or directed the research and was corresponding author. This paper was the first to demonstrate that survivin is phosphorylated by aurora-B in vivo and that a phosphomimic, which turns over rapidly at the centromeres (FRAP analysis), cannot correctly biorient chromosomes during mitosis or support cell proliferation.Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2012-02-06Usage metrics
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