Survivin modulates microtubule dynamics and nucleation throughout the cell cycle.
Mol Biol Cell
; 17(3): 1483-93, 2006 Mar.
Article
em En
| MEDLINE
| ID: mdl-16407408
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.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Ciclo Celular
/
Proteínas Associadas aos Microtúbulos
/
Microtúbulos
/
Proteínas de Neoplasias
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Biol Cell
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos