Tip60 is a nuclear hormone receptor coactivator
Tip60 is a nuclear hormone receptor coactivator
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DOI：
10.1074/jbc.274.25.17599
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发表时间：
1999-06-18
影响因子：
4.8
通讯作者：
Robson, CN
中科院分区：
文献类型：
--
作者：
Brady, ME;Ozanne, DM;Robson, CN
雄激素受体（AR）是核激素受体超家族的一员，近年来该领域的工作主要集中在确定该超家族成员所要求的转录控制机制。利用酵母双杂交筛选人类AR的cooh末端区域，我们鉴定出Tip60是一个AR相互作用蛋白。在本报告中，我们发现Tip60，最初被鉴定为人类免疫缺陷病毒TAT蛋白的辅激活因子，可以在LNCaP和COS-1细胞系中以配体依赖的方式增强ar介导的交易激活。此外，我们的实验表明，Tip60还可以通过配体依赖的方式增强雌激素受体和孕激素受体的转激活；我们的研究还表明，Tip60在体外与全长AR共免疫沉淀，并且在我们的系统中，Tip60将转激活提高到与类固醇受体共激活因子1、p300和creb结合蛋白共激活的水平。这些蛋白在增强核激素受体介导的转录激活中的重要性被广泛接受，这项工作表明Tip60可能发挥同样重要的作用。
The androgen receptor (AR) is a member of the nuclear hormone receptor superfamily, Recent work in this field has been focused upon defining the mechanisms of transcriptional control exacted by members of this superfamily. Using a COOH-terminal region of the human AR in a yeast two-hybrid screen, we have identified Tip60 as an AR-interacting protein. In this report, we show that Tip60, which was originally identified as a coactivator for the human immunodeficiency virus TAT protein, can enhance AR-mediated transactivation in a ligand-dependent manner in LNCaP and COS-1 cell lines. In addition, our experiments show that Tip60 can also enhance transactivation through the estrogen receptor and progesterone receptor in a ligand-dependent manner; thus identifying Tip60 as a nuclear hormone receptor coactivator, Our studies also demonstrate that Tip60 co-immunoprecipitates with the full-length AR in vitro and that, in our system, Tip60 enhances transactivation to levels observed with the coactivators steroid receptor coactivator 1, p300, and CREB-binding protein. The importance of such proteins in enhancing nuclear hormone receptor-mediated transcriptional activation is widely accepted, and this work suggests that Tip60 may have an equally important role to play.