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.
Written by:
Fadri-Moskwik M, Weiderhold KN, Deeraksa A, Chuang C, Pan J, Lin SH, Yu-Lee LY. Are you the author?
Department of Medicine – IAR Section, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
Reference: FASEB J. 2012 Jul 19. Epub ahead of print.
doi: 10.1096/fj.12-206656
PubMed Abstract
PMID: 22751009
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