title: Survivin modulates microtubule dynamics and nucleation throughout the cell cycle.
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.
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Jack
authors.initials: J
authors.lastname: Rosa
authors.forename: Pedro
authors.initials: P
authors.lastname: Canovas
authors.forename: Ashraful
authors.initials: A
authors.lastname: Islam
authors.forename: Dario C
authors.initials: DC
authors.lastname: Altieri
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Doxsey
mesh_terms: D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D019556:COS Cells; D002453:Cell Cycle; D002478:Cells, Cultured; D018385:Centrosome / Q000378:metabolism; D002522:Chlorocebus aethiops; D048749:Cytokinesis; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D007399:Interphase / Q000502:physiology; D008869:Microtubule-Associated Proteins / Q000172:deficiency / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology; D009363:Neoplasm Proteins / Q000172:deficiency / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000172:deficiency; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D000077022:Survivin; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases