A-kinase anchoring protein 12 regulates the completion of cytokinesis

被引:13
作者
Choi, Moon-Chang [2 ]
Lee, Yang-Ui [2 ]
Kim, Sung-Hak [2 ]
Park, Jung-Hyun [2 ]
Kim, Hyun-Ah [2 ]
Oh, Do-Youn [1 ,2 ]
Im, Seock-Ah [1 ,2 ]
Kim, Tae-You [1 ,2 ]
Jong, Hyun-Soon [2 ]
Bang, Yung-Jue [1 ,2 ]
机构
[1] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 110799, South Korea
[2] Canc Res Inst, Natl Res Lab Canc Epigenet, Seoul, South Korea
基金
新加坡国家研究基金会;
关键词
AKAP; AKAP12; gravin; cytokinesis; MLCK; ML-9;
D O I
10.1016/j.bbrc.2008.05.184
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
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. (C) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:85 / 89
页数:5
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