Aurora A kinase activity is required to maintain an active spindle assembly checkpoint during prometaphase.
J Cell Sci
; 131(7)2018 04 12.
Article
en En
| MEDLINE
| ID: mdl-29555820
ABSTRACT
During the prometaphase stage of mitosis, the cell builds a bipolar spindle of microtubules that mechanically segregates sister chromatids between two daughter cells in anaphase. The spindle assembly checkpoint (SAC) is a quality control mechanism that monitors proper attachment of microtubules to chromosome kinetochores during prometaphase. Segregation occurs only when each chromosome is bi-oriented with each kinetochore pair attached to microtubules emanating from opposite spindle poles. Overexpression of the protein kinase Aurora A is a feature of various cancers and is thought to enable tumour cells to bypass the SAC, leading to aneuploidy. Here, we took advantage of a chemical and chemical-genetic approach to specifically inhibit Aurora A kinase activity in late prometaphase. We observed that a loss of Aurora A activity directly affects SAC function, that Aurora A is essential for maintaining the checkpoint protein Mad2 on unattached kinetochores and that inhibition of Aurora A leads to loss of the SAC, even in the presence of nocodazole or Taxol. This is a new finding that should affect the way Aurora A inhibitors are used in cancer treatments.This article has an associated First Person interview with the first authors of the paper.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Prometafase
/
Puntos de Control de la Fase M del Ciclo Celular
/
Aurora Quinasa A
/
Proteínas Mad2
Límite:
Humans
Idioma:
En
Revista:
J Cell Sci
Año:
2018
Tipo del documento:
Article
País de afiliación:
Francia