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

作者：Fadri Moskwik Maria; Weiderhold Kimberly N; Deeraksa Arpa****; Chuang Carol; Pan Jing; Lin Sue Hwa; Yu Lee Li Yuan^*

来源：The FASEB Journal, 2012, 26(10): 4057-4067.

DOI：10.1096/fj.12-206656

• HDAC3
• mitotic spindle
• kinetochore-microtubule attachment
• post-translational modification

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 %26lt; 0.01 and P %26lt; 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

• 出版日期2012-10