QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 17, Issue 4, 1897-1909, April 2006

This Article Full Text Full Text (PDF) Supplemental Material All Versions of this Article: E05-08-0727v1 17/4/1897    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lens, S. M.A. Articles by Medema, R. H. Search for Related Content PubMed PubMed Citation Articles by Lens, S. M.A. Articles by Medema, R. H.

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

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

^* Department of Medical Oncology, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands; Department of Medical Oncology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands

Submitted August 5, 2005; Revised January 11, 2006; Accepted January 17, 2006
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 whether 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 baculovirus IAP repeat (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 they 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.

Abbreviations used: BIR, baculovirus IAP repeat; CPC, chromosomal passenger complex.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

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

This article has been cited by other articles:

				S. Gao, M. G. Giansanti, G. J. Buttrick, S. Ramasubramanyan, A. Auton, M. Gatti, and J. G. Wakefield Australin: a chromosomal passenger protein required specifically for Drosophila melanogaster male meiosis J. Cell Biol., February 6, 2008; 180(3): 521 - 535. [Abstract] [Full Text] [PDF]

				E. Bourhis, S. G. Hymowitz, and A. G. Cochran The Mitotic Regulator Survivin Binds as a Monomer to Its Functional Interactor Borealin J. Biol. Chem., November 30, 2007; 282(48): 35018 - 35023. [Abstract] [Full Text] [PDF]

				G. Vader, C. W.A. Cruijsen, T. van Harn, M. J.M. Vromans, R. H. Medema, and S. M.A. Lens The Chromosomal Passenger Complex Controls Spindle Checkpoint Function Independent from Its Role in Correcting Microtubule Kinetochore Interactions Mol. Biol. Cell, November 1, 2007; 18(11): 4553 - 4564. [Abstract] [Full Text] [PDF]

				G. Vader, R. H. Medema, and S. M.A. Lens The chromosomal passenger complex: guiding Aurora-B through mitosis J. Cell Biol., June 19, 2006; 173(6): 833 - 837. [Abstract] [Full Text] [PDF]

				U. R. Klein, E. A. Nigg, and U. Gruneberg Centromere Targeting of the Chromosomal Passenger Complex Requires a Ternary Subcomplex of Borealin, Survivin, and the N-Terminal Domain of INCENP Mol. Biol. Cell, June 1, 2006; 17(6): 2547 - 2558. [Abstract] [Full Text] [PDF]