TY - JOUR
T1 - Aurora B is regulated by acetylation/deacetylation during mitosis in prostate cancer cells
AU - Fadri-Moskwik, Maria
AU - Weiderhold, Kimberly N.
AU - Deeraksa, Arpaporn
AU - Chuang, Carol
AU - Pan, Jing
AU - Lin, Sue Hwa
AU - Yu-Lee, Li Yuan
PY - 2012/10
Y1 - 2012/10
N2 - 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.
AB - 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.
KW - HDAC3
KW - Kinetochore-microtubule attachment
KW - Mitotic spindle
KW - Post-translational modification
UR - http://www.scopus.com/inward/record.url?scp=84868087355&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84868087355&partnerID=8YFLogxK
U2 - 10.1096/fj.12-206656
DO - 10.1096/fj.12-206656
M3 - Article
C2 - 22751009
AN - SCOPUS:84868087355
SN - 0892-6638
VL - 26
SP - 4057
EP - 4067
JO - FASEB Journal
JF - FASEB Journal
IS - 10
ER -