Survivin modulates microtubule dynamics and nucleation throughout the cell cycle
UMass Chan Affiliations
Department of Cancer BiologyProgram in Molecular Medicine
Graduate School of Biomedical Sciences
Document Type
Journal ArticlePublication Date
2006-01-13Keywords
Animals; COS Cells; *Cell Cycle; Cells, Cultured; Centrosome; Cercopithecus aethiops; Cytokinesis; Humans; Interphase; Microtubule-Associated Proteins; Microtubules; Mitosis; Neoplasm Proteins; Protein-Serine-Threonine Kinases; RNA Interference; Recombinant Fusion ProteinsLife Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
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.Source
Mol Biol Cell. 2006 Mar;17(3):1483-93. Epub 2006 Jan 11. Link to article on publisher's siteDOI
10.1091/mbc.E05-08-0723Permanent Link to this Item
http://hdl.handle.net/20.500.14038/32452PubMed ID
16407408Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1091/mbc.E05-08-0723