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Vol. 17, Issue 3, 1483-1493, March 2006

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Survivin Modulates Microtubule Dynamics and Nucleation throughout the Cell Cycle

Jack Rosa ^*, Pedro Canovas , Ashraful Islam , Dario C. Altieri  , and Stephen J. Doxsey ^* 

^* Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605; Department of Cancer Biology and the Cancer Center, University of Massachusetts Medical School, Worcester, MA 01605

Submitted August 5, 2005; Revised November 28, 2005; Accepted January 3, 2006
Monitoring Editor: Ted Salmon

Survivin is a member of the chromosomal passenger complex implicated in kinetochore attachment, bipolar spindle formation, and cytokinesis. However, the mechanism by which survivin modulates these processes is unknown. Here, we show by time-lapse imaging of cells expressing either green fluorescent protein (GFP)--tubulin or the microtubule plus-end binding protein GFP-EB1 that depletion of survivin by small interfering RNAs (siRNAs) increased both the number of microtubules nucleated by centrosomes and the incidence of microtubule catastrophe, the transition from microtubule growth to shrinking. In contrast, survivin overexpression reduced centrosomal microtubule nucleation and suppressed both microtubule dynamics in mitotic spindles and bidirectional growth of microtubules in midbodies during cytokinesis. siRNA depletion or pharmacologic inhibition of another chromosomal passenger protein Aurora B, had no effect on microtubule dynamics or nucleation in interphase or mitotic cells even though mitosis was impaired. We propose a model in which survivin modulates several mitotic events, including spindle and interphase microtubule organization, the spindle assembly checkpoint and cytokinesis through its ability to modulate microtubule nucleation and dynamics. This pathway may affect the microtubule-dependent generation of aneuploidy and defects in cell polarity in cancer cells, where survivin is commonly up-regulated.

Abbreviations used: IAP, inhibitor of apoptosis.

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

These authors contributed equally to this work.

Address correspondence to: Stephen Doxsey (stephen.doxsey{at}umassmed.edu).

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