曲古抑菌素A通过激活蛋白1（AP1）位点激活骨桥蛋白基因启动子。

Trichostatin A activates the osteopontin gene promoter through AP1 site.

作者信息

Sakata Ryosuke, Minami Shinji, Sowa Yoshihiro, Yoshida Munehito, Tamaki Tetsuya

机构信息

Department of Orthopedic Surgery, Wakayama Medical University, 811-1, Wakayama 641-8510, Japan.

出版信息

Biochem Biophys Res Commun. 2004 Mar 19;315(4):959-63. doi: 10.1016/j.bbrc.2004.01.152.

DOI:10.1016/j.bbrc.2004.01.152

PMID:14985105

Abstract

In this study, we investigated osteoblastic differentiation by trichostatin A (TSA), a histone deacetylase inhibitor in mouse undifferentiated mesenchymal cell line. TSA increased the osteopontin (OPN) mRNA level and OPN protein. Deletion analysis of the promoter region revealed TSA-induced luciferase response was regulated by -75 to -65 of the OPN promoter. There was an AP1-binding sequence at the site of the OPN promoter. In an electrophoretic mobility shift assay, bands of the complexes were supershifted by addition of antibody to c-fos and phosphorylated c-jun. These data suggested that AP1 plays a crucial role in the TSA-induced OPN expression.

摘要

在本研究中，我们利用组蛋白脱乙酰酶抑制剂曲古抑菌素A（TSA）对小鼠未分化间充质细胞系中的成骨细胞分化进行了研究。TSA提高了骨桥蛋白（OPN）的mRNA水平和OPN蛋白水平。对启动子区域的缺失分析显示，TSA诱导的荧光素酶反应受OPN启动子-75至-65区域调控。在OPN启动子该位点存在一个AP1结合序列。在电泳迁移率变动分析中，加入抗c-fos和磷酸化c-jun抗体后，复合物条带出现超迁移。这些数据表明，AP1在TSA诱导的OPN表达中起关键作用。