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MBC in Press, published online ahead of print January 25, 2006
Mol. Biol. Cell 10.1091/mbc.E05-08-0727

A more recent version of this article appeared on April 1, 2006
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Submitted on August 5, 2005
Revised on January 11, 2006
Accepted on January 17, 2006

Uncoupling the Central Spindle-associated Function of the Chromosomal Passenger Complex from Its Role at Centromeres

Susanne M.A. Lens,*{dagger} Jose A. Rodriguez,{ddagger} Gerben Vader,*{dagger} Simone W. Span,{ddagger} Giuseppe Giaccone,{ddagger} and René H. Medema*{dagger}

*Division of Molecular Biology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; {ddagger}Department of Medical Oncology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands

Monitoring Editor: Ted Salmon

Survivin is a component of the Chromosomal Passenger Complex (CPC) that plays a role in maintenance of an active spindle checkpoint and in cytokinesis. To study if these different functions can be attributed to distinct domains within the Survivin protein, we complemented Survivin-depleted cells with a variety of point- and deletion-mutants of Survivin. We show that an intact BIR domain is required for proper spindle checkpoint functioning, but dispensable for cytokinesis. In line with this, mutants lacking an intact BIR domain localized normally to the central spindle, but their localization to inner centromeres was severely perturbed. Consequently, these mutants failed to recruit Aurora B, Borealin/Dasra B and BubR1 to centromeres and kinetochores, but had retained the ability to recruit Aurora B and Borealin/Dasra B to the midzone and midbody. Thus the C-terminus of Survivin is sufficient for central spindle localization and execution of cytokinesis, but the additional presence of a functional BIR domain is essential for centromere targeting and spindle checkpoint function. Importantly, our data show that the function of the CPC at the centromere can be separated from its function at the central spindle, and that execution of cytokinesis does not require prior concentration of the CPC at centromeres.

{dagger}Present address: University Medical Center Utrecht, Department of Medical Oncology, Location Stratenum, Str. 2.103, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands.

Address correspondence to: Susanne M.A. Lens (s.m.a.lens{at}med.uu.nl)




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