CENP-E kinesin interacts with SKAP protein to orchestrate accurate chromosome segregation in mitosis.
J Biol Chem
; 287(2): 1500-9, 2012 Jan 06.
Article
em En
| MEDLINE
| ID: mdl-22110139
ABSTRACT
Mitotic chromosome segregation is orchestrated by the dynamic interaction of spindle microtubules with the kinetochore. Although previous studies show that the mitotic kinesin CENP-E forms a link between attachment of the spindle microtubule to the kinetochore and the mitotic checkpoint signaling cascade, the molecular mechanism underlying dynamic kinetochore-microtubule interactions in mammalian cells remains elusive. Here, we identify a novel interaction between CENP-E and SKAP that functions synergistically in governing dynamic kinetochore-microtubule interactions. SKAP binds to the C-terminal tail of CENP-E in vitro and is essential for an accurate kinetochore-microtubule attachment in vivo. Immunoelectron microscopic analysis indicates that SKAP is a constituent of the kinetochore corona fibers of mammalian centromeres. Depletion of SKAP or CENP-E by RNA interference results in a dramatic reduction of inter-kinetochore tension, which causes chromosome mis-segregation with a prolonged delay in achieving metaphase alignment. Importantly, SKAP binds to microtubules in vitro, and this interaction is synergized by CENP-E. Based on these findings, we propose that SKAP cooperates with CENP-E to orchestrate dynamic kinetochore-microtubule interaction for faithful chromosome segregation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Cromossômicas não Histona
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Cromossomos Humanos
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Cinetocoros
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Proteínas de Ciclo Celular
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Segregação de Cromossomos
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Proteínas Associadas aos Microtúbulos
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Mitose
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article