Regulation of microtubule stability and mitotic progression by survivin.
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.
Giodini
Alessandra
A
Boyer Center for Molecular Medicine, Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06536, USA.
Kallio
Marko J
MJ
Wall
Nathan R
NR
Gorbsky
Gary J
GJ
Tognin
Simona
S
Marchisio
Pier Carlo
PC
Symons
Marc
M
Altieri
Dario C
DC
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
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