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A more recent version of this article appeared on March 1, 2006
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Submitted on August 5, 2005
Revised on November 28, 2005
Accepted on January 3, 2006
*Program in Molecular Medicine and Department of Cancer Biology and the Cancer Center, University of Massachusetts Medical School, Worcester, MA 01605
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 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 catstrophe, 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.
These authors contributed equally to this work.
Address correspondence to:
Stephen J. Doxsey (stephen.doxsey{at}umassmed.edu)
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