title: Aurora B is regulated by acetylation/deacetylation during mitosis in prostate cancer cells.
abstract: 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.
authors: Department of Medicine-IAR Section, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
authors: Maria
authors: M
authors: Fadri-Moskwik
authors: Kimberly N
authors: KN
authors: Weiderhold
authors: Arpaporn
authors: A
authors: Deeraksa
authors: Carol
authors: C
authors: Chuang
authors: Jing
authors: J
authors: Pan
authors: Sue-Hwa
authors: SH
authors: Lin
authors: Li-Yuan
authors: LY
authors: Yu-Lee
mesh_terms: D000107:Acetylation; D064107:Aurora Kinase B; D064127:Aurora Kinases; D045744:Cell Line, Tumor; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D018386:Kinetochores / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000099186:Histone Deacetylase 3
chemical_list: D064107:Aurora Kinase B; D064127:Aurora Kinases; D006655:Histone Deacetylases; D017346:Protein Serine-Threonine Kinases; D000099186:Histone Deacetylase 3; C576921:AURKB protein, human