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Aurora B is regulated by acetylation/deacetylation during mitosis in prostate cancer cells
Author(s) -
FadriMoskwik Maria,
Weiderhold Kimberly N.,
Deeraksa Arpaporn,
Chuang Carol,
Pan Jing,
Lin SueHwa,
YuLee LiYuan
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.12-206656
Subject(s) - aurora b kinase , acetylation , mitosis , kinetochore , aurora inhibitor , aurora a kinase , prometaphase , microtubule , aurora kinase , chemistry , microbiology and biotechnology , biology , cell cycle , biochemistry , cancer , genetics , chromosome , gene
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