Identification of a Transactivation Function in the Progesterone Receptor That Interacts with the TAFII110 Subunit of the TFIID Complex (*)-猫眼课题宝

黄体酮受体中与 TFIID 复合物的 TAFII110 亚基相互作用的反式激活功能的鉴定 (*)

DOI：

发表时间：

1995

期刊：

Journal of Biological Chemistry

影响因子：

4.8

通讯作者：

中科院分区：

生物学2区

文献类型：

作者：

C. Schwerk;M. Klotzbücher;M. Sachs;V. Ulber;L. Klein

人孕酮受体对靶基因的转录激活被认为涉及孕酮受体和一般转录因子之间的直接或间接的蛋白质-蛋白质相互作用。通用转录因子 TFIID 在转录中发挥关键作用，它是一种由 TATA 结合蛋白和几个紧密相关因子 (TAF) 组成的多蛋白复合物。 TAF 已被证明是激活转录所必需的，因此是激活蛋白的潜在靶标。通过体外相互作用测定，我们可以确定孕酮受体和 TATA 结合蛋白相关因子 dTAFII110 之间的特异性相互作用。负责相互作用的 dTAFII110 结构域与报道的足以结合 Sp1 的结构域不同。有些令人惊讶的是，缺失分析表明，先前确定的孕酮受体激活功能 1 和 2 并不是这种相互作用所必需的，但指出了 DNA 结合结构域的重要作用。在共转染实验和体外转录测定中，黄体酮受体的 DNA 结合域显示出显着的激活潜力。这些发现综合起来表明，黄体酮受体和 TAFII110 之间的相互作用可能代表了激活机制中的重要一步。

Transcriptional activation of target genes by the human progesterone receptor is thought to involve direct or indirect protein-protein interactions between the progesterone receptor and general transcription factors. A key role in transcription plays the general transcription factor TFIID, a multiprotein complex consisting of the TATA-binding protein and several tightly associated factors (TAFs). TAFs have been shown to be required for activated transcription and are, thus, potential targets of activator proteins. Using in vitro interaction assays, we could identify specific interactions between the progesterone receptor and the TATA-binding protein-associated factor dTAFII110. The dTAFII110 domain responsible for the interaction is distinct from that reported to suffice for binding to Sp1. Somewhat surprisingly, deletion analysis indicated that the previously identified activation functions 1 and 2 of the progesterone receptor are not required for this interaction but pointed to an important role of the DNA binding domain. In cotransfection experiments and an in vitro transcription assay, the DNA binding domain of the progesterone receptor displayed significant activation potential. These findings, taken together, suggest that an interaction between the progesterone receptor and TAFII110 may represent an important step in the mechanism of activation.