Transcriptional coactivation of bone-specific transcription factor Cbfa1 by TAZ
Transcriptional coactivation of bone-specific transcription factor Cbfa1 by TAZ
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DOI：
10.1128/mcb.23.3.1004-1013.2003
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发表时间：
2003-02-01
影响因子：
5.3
通讯作者：
Aukhil, I
中科院分区：
文献类型：
--
作者：
Cui, CB;Cooper, LF;Aukhil, I
核心结合因子1(Cbfa1；又称Runx2)是一种转录因子，属于转录因子家族，与成骨细胞特异性顺式作用元件(OSE2)结合，激活成骨细胞特异性基因骨钙素的表达。利用酵母双杂交系统，我们鉴定了一个与Cbfa1结合的转录共激活因子TAZ(转录共激活因子与PDZ结合基序)。Cbfa1与TAZ的免疫共沉淀，以及TAZ通过Cbfa1诱导骨钙素启动子-荧光素酶活性的剂量依赖性增加，证实了Cbfa1与TAZ之间的功能关系。NIH3T3、MC 3T3和ROS17/2.8细胞表现出预期的Cbfa1的核定位，而TAZ在Cbfa1或TAZ的转染下分布于细胞质中，并有一定的核定位。在Cbfa1和TAZ的共同作用下，转染组的TAZ表现出明显的核定位。当与Cbfa1共转染时，TAZ的显性-负性结构显示出最小的核定位。这些数据表明，TAZ是Cbfa1的转录共激活因子，可能参与成骨细胞分化的调节。
Core-binding factor 1 (Cbfa1; also called Runx2) is a transcription factor belonging to the Runt family of transcription factors that binds to an osteoblast-specific cis-acting element (OSE2) activating the expression of osteocalcin, an osteoblast-specific gene. Using the yeast two-hybrid system, we identified a transcriptional coactivator, TAZ (transcriptional coactivator with PDZ-binding motif), that binds to Cbfa1. A functional relationship between Cbfa1 and TAZ is demonstrated by the coimmunoprecipitation of TAZ by Cbfa1 and by the fact that TAZ induces a dose-dependent increase in the activity of osteocalcin promoter-luciferase constructs by Cbfa1 A dominant-negative construct of TAZ in which the coactivation domains have been deleted reduces osteocalcin gene expression down to basal levels. NIH 3T3, MC 3T3, and ROS 17/2.8 cells showed the expected nuclear localization of Cbfa1, whereas TAZ was distributed throughout the cytoplasm with some nuclear localization when transfected with either Cbfa1 or TAZ. Upon cotransfection by both Cbfa1 and TAZ, the transfected TAZ shows predominant nuclear localization. The dominant-negative construct of TAZ shows minimal nuclear localization upon cotransfection with Cbfa1. These data indicate that TAZ is a transcription coactivator for Cbfa1 and may be involved in the regulation of osteoblast differentiation.