A-kinase anchoring protein 12 regulates the completion of cytokinesis.
A-kinase anchoring protein 12 (AKAP12) gene is frequently inactivated in human gastric cancer and in several other cancers due to promoter hypermethylation. However, the biological function of AKAP12 in tumorigenesis remains to be identified. Aneuploidy, a hallmark of cancer cells, is often caused by abnormal cell division. In the present study, AKAP12 was found to localize to the cell periphery during interphase and to the actomyosin contractile ring during cytokinesis. Furthermore, AKAP12 depletion using small interfering RNA increased the number of multinucleated cells, and disrupted the completion of cytokinesis. Interestingly, the inhibition of myosin light chain kinase (MLCK), a key regulator of actomyosin contractility, removed AKAP12 from the cell periphery during interphase and from the contractile ring during cytokinesis, suggesting that AKAP12 might be a downstream effector of MLCK. Our findings implicate AKAP12 in the regulation of cytokinesis progression, and suggest a novel role for AKAP12 tumor suppressor.
National Research Laboratory for Cancer Epigenetics, Cancer Research Institute, Seoul, Republic of Korea.
Moon-Chang
MC
Choi
Yang-Ui
YU
Lee
Sung-Hak
SH
Kim
Jung-Hyun
JH
Park
Hyun-Ah
HA
Kim
Do-Youn
DY
Oh
Seock-Ah
SA
Im
Tae-You
TY
Kim
Hyun-Soon
HS
Jong
Yung-Jue
YJ
Bang
D054758:A Kinase Anchor Proteins / Q000235:genetics / Q000378:metabolism*; D000205:Actomyosin / Q000378:metabolism; D002452:Cell Count; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D048749:Cytokinesis / Q000235:genetics; D015726:Giant Cells / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D007399:Interphase; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D034622:RNA Interference; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D054758:A Kinase Anchor Proteins; C491162:AKAP12 protein, human; D018797:Cell Cycle Proteins; D025521:Tumor Suppressor Proteins; D000205:Actomyosin; D009219:Myosin-Light-Chain Kinase