Phosphorylation by aurora-B negatively regulates survivin function during mitosis

Wheatley, Sally P, Barrett, Rachel M, Andrews, Paul D, Medema, Rene H, Morley, Simon J, Swedlow, Jason R and Lens, Susanne M A (2007) Phosphorylation by aurora-B negatively regulates survivin function during mitosis. Cell Cycle, 6 (10). pp. 1220-1230. ISSN 1538-4101

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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.

Item Type: Article
Additional Information: 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.
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Depositing User: Sally Paula Wheatley
Date Deposited: 06 Feb 2012 19:51
Last Modified: 30 Mar 2012 11:56
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