Survivin modulates microtubule dynamics and nucleation throughout the cell cycle
Graduate School of Biomedical Sciences; Program in Molecular Medicine; Department of Cancer Biology
Life Sciences | Medicine and Health Sciences
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)-alpha-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.
DOI of Published Version
Mol Biol Cell. 2006 Mar;17(3):1483-93. Epub 2006 Jan 11. Link to article on publisher's site
Molecular biology of the cell
Rosa, Jack; Canovas, Pedro; Islam, Ashraful; Altieri, Dario C.; and Doxsey, Stephen J., "Survivin modulates microtubule dynamics and nucleation throughout the cell cycle" (2006). GSBS Student Publications. 1021.