title: Regulation of microtubule stability and mitotic progression by survivin.
abstract: Survivin is a member of the inhibitor of apoptosis (IAP) gene family, which has been implicated in both preservation of cell viability and regulation of mitosis in cancer cells. Here, we show that HeLa cells microinjected with a polyclonal antibody to survivin exhibited delayed progression in prometaphase (31.5 +/- 6.9 min) and metaphase (126.8 +/- 73.8 min), as compared with control injected cells (prometaphase, 21.5 +/- 3.3 min; metaphase, 18.9 +/- 4.5 min; P < 0.01). Cells injected with the antibody to survivin displayed short mitotic spindles severely depleted of microtubules and occasionally underwent apoptosis without exiting the mitotic block or thereafter. Forced expression of survivin in HeLa cells profoundly influenced microtubule dynamics with reduction of pole-to-pole distance at metaphase (8.57 +/- 0.21 microm versus 10.58 +/- 0.19 microm; P < 0.0001) and stabilization of microtubules against nocodazole-induced depolymerization in vivo. These data demonstrate that survivin functions at cell division to control microtubule stability and assembly of a normal mitotic spindle. This pathway may facilitate checkpoint evasion and promote resistance to chemotherapy in cancer.
authors: Boyer Center for Molecular Medicine, Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06536, USA.
authors: Alessandra
authors: A
authors: Giodini
authors: Marko J
authors: MJ
authors: Kallio
authors: Nathan R
authors: NR
authors: Wall
authors: Gary J
authors: GJ
authors: Gorbsky
authors: Simona
authors: S
authors: Tognin
authors: Pier Carlo
authors: PC
authors: Marchisio
authors: Marc
authors: M
authors: Symons
authors: Dario C
authors: DC
authors: Altieri
mesh_terms: D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology; D051034:Inhibitor of Apoptosis Proteins; D008845:Microinjections; D008869:Microtubule-Associated Proteins; D008870:Microtubules / Q000502:physiology*; D008938:Mitosis / Q000502:physiology*; D009363:Neoplasm Proteins; D008941:Spindle Apparatus / Q000502:physiology; D000077022:Survivin; D014162:Transfection
chemical_list: C107489:BIRC5 protein, human; D002868:Chromosomal Proteins, Non-Histone; D007074:Immunoglobulin G; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin