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Phosphorylation by Aurora-B Negatively Regulates Survivin Function During Mitosis

Sally P. Wheatley, Rachel M. Barrett, Paul D. Andrews, Rene H. Medema, Simon J. Morley, Jason R. Swedlow and Susanne M.A. Lens

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Survivin 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.

Authors

Sally P. Wheatley

University of Sussex, Brighton, UK

Rachel M. Barrett

University of Sussex, Brighton, UK

Paul D. Andrews

University of Dundee, Dundee, UK

Rene H. Medema

University Medical Center Utrecht, Utrecht, The Netherlands

Simon J. Morley

University of Sussex, Brighton, UK

Jason R. Swedlow

University of Dundee, Dundee, UK

Susanne M.A. Lens

University Medical Center Utrecht, Utrecht, The Netherlands

This is an open-access article

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.