Aurora B is regulated by acetylation/deacetylation during mitosis in prostate cancer cells

Article

关键词: CHROMOSOMAL PASSENGER COMPLEX;    HISTONE DEACETYLASE INHIBITORS;    SMALL-MOLECULE INHIBITOR;    MITOTIC SPINDLE;    LYSINE ACETYLATION;    PROTEIN COMPLEXES;    KINASE-ACTIVITY;    KINETOCHORE;    PHOSPHORYLATION;    MICROTUBULES;   

DOI  :  10.1096/fj.12-206656

来源: SCIE

【 摘 要 】

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.-Fadri-Moskwik, M., Weiderhold, K. N., Deeraksa, A., Chuang, C., Pan, J., Lin, S.-H., Yu-Lee, L.-Y. Aurora B is regulated by acetylation/deacetylation during mitosis in prostate cancer cells. FASEB J. 26, 4057-4067 (2012). www.fasebj.org

【 授权许可】

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