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    Survivin modulates microtubule dynamics and nucleation throughout the cell cycle

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    Authors
    Rosa, Jack
    Canovas, Pedro
    Islam, Ashraful
    Altieri, Dario C.
    Doxsey, Stephen J.
    UMass Chan Affiliations
    Department of Cancer Biology
    Program in Molecular Medicine
    Graduate School of Biomedical Sciences
    Document Type
    Journal Article
    Publication Date
    2006-01-13
    Keywords
    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 Proteins
    Life Sciences
    Medicine and Health Sciences
    
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    Link to Full Text
    http://dx.doi.org/10.1091/mbc.E05-08-0723
    Abstract
    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 site
    DOI
    10.1091/mbc.E05-08-0723
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/32452
    PubMed ID
    16407408
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1091/mbc.E05-08-0723
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