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Aurora B is regulated by dynamic acetylation/deacetylation in prostate cancer cells
Author(s) -
Fadri-Moskwik Maria Theresa Morato,
Weiderhold Kim,
Chuang Carol,
Deeraksa Arpaporn,
Pan Jing,
Lin Sue-Hwa,
Yu-Lee Li-Yuan
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/fasebj.26.1_supplement.lb212
Subject(s) - acetylation , aurora b kinase , aurora a kinase , mitosis , kinetochore , aurora inhibitor , spindle apparatus , chemistry , microbiology and biotechnology , aurora kinase , prometaphase , biology , cell cycle , biochemistry , apoptosis , cell division , cell , chromosome , gene
Protein acetylation has been implicated to play a role during mitosis, but the targets remain to be explored. Aurora B kinase plays a crucial role in mitosis and posttranslational modifications of Aurora B are known to regulate its kinase activity, localization and function. Whether acetylation also regulates Aurora B activity is not known. Using PC3 prostate cancer cells, we found that Aurora B is acetylated in mitosis and undergoes rapid acetylation/deacetylation, with peak deacetylation occurring in prometaphase. We found that HDAC3, a deacetylase that was previously shown by our laboratory to localize to the mitotic spindle and regulate spindle stability, is associated with Aurora B by co‐immunoprecipitation. Knockdown of HDAC3 or inhibiting HDAC3 activity with a small molecule inhibitor apicidin led to a higher level of Aurora B acetylation. Increased Aurora B acetylation is correlated with reduced Aurora B kinase activity that resulted in defects in Aurora B‐dependent mitotic processes, including kinetochore‐microtubule attachment and chromosome congression. Thus, our studies suggest that Aurora B kinase activity and function are regulated by dynamic acetylation/deacetylation in mitotic prostate cancer cells. Funded by NIH/NIGMS # K12 GM084897 (MFM), D.L. Duncan Cancer Center and Alkek Award for Experimental Therpeutics (Ly YL), PC080847, PC093132(SHL)