Aurora B is regulated by acetylation/deacetylation during mitosis in prostate cancer cells.
FASEB J
; 26(10): 4057-67, 2012 Oct.
Article
em En
| MEDLINE
| ID: mdl-22751009
ABSTRACT
Protein acetylation has been implicated in playing an important role during mitotic progression. Aurora B kinase is known to play a critical role in mitosis. However, whether Aurora B is regulated by acetylation is not known. Using IP with an anti-acetyl lysine antibody, we identified Aurora B as an acetylated protein in PC3 prostate cancer cells. Knockdown of HDAC3 or inhibiting HDAC3 deacetylase activity led to a significant increase (P<0.01 and P<0.05, respectively) in Aurora B acetylation as compared to siLuc or vehicle-treated controls. Increased Aurora B acetylation is correlated with a 30% reduction in Aurora B kinase activity in vitro and resulted in significant defects in Aurora B-dependent mitotic processes, including kinetochore-microtubule attachment and chromosome congression. Furthermore, Aurora B transiently interacts with HDAC3 at the kinetochore-microtubule interface of congressing chromosomes during prometaphase. This window of interaction corresponded with a transient but significant reduction (P=0.02) in Aurora B acetylation during early mitosis. Together, these results indicate that Aurora B is more active in its deacetylated state and further suggest a new mechanism by which dynamic acetylation/deacetylation acts as a rheostat to fine-tune Aurora B activity during mitotic progression.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
/
Proteínas Serina-Treonina Quinases
/
Mitose
Limite:
Humans
/
Male
Idioma:
En
Revista:
FASEB J
Assunto da revista:
BIOLOGIA
/
FISIOLOGIA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos