A subfamily of RNA-binding DEAD-box proteins acts as an estrogen receptor alpha coactivator through the N-terminal activation domain (AF-1) with an RNA coactivator, SRA.
A subfamily of RNA-binding DEAD-box proteins acts as an estrogen receptor alpha coactivator through the N-terminal activation domain (AF-1) with an RNA coactivator, SRA.
复制标题
DOI：
--
复制
发表时间：
2001
期刊：
影响因子：
--
通讯作者：
M. Watanabe;J. Yanagisawa;H. Kitagawa;K. Takeyama;S. Ogawa;Y. Arao;M. Suzawa;Y. Kobayashi;T. Yano;H. Yoshikawa;Y. Masuhiro;S. Kato
中科院分区：
文献类型：
--
作者：
M. Watanabe;J. Yanagisawa;H. Kitagawa;K. Takeyama;S. Ogawa;Y. Arao;M. Suzawa;Y. Kobayashi;T. Yano;H. Yoshikawa;Y. Masuhiro;S. Kato
一类核受体AF-2辅激活因子复合物含有SRC-1/TIF 2家族CBP/p300和RNA辅激活因子SRA。我们确定了RNA结合的DEAD盒蛋白（p72/p68）的一个亚家族作为一个人雌激素受体α（hER α）的辅激活剂在复杂的含有这些因素。p72/p68与任何SRC-1/TIF 2家族蛋白的AD 2和hER α A/B结构域相互作用，但不与任何其他测试的核受体相互作用。p72/p68、TIF 2（SRC-1）和SRA与MCF 7细胞中的雌激素结合的hER α以及与来自HeLa核提取物的hER α相关的部分纯化的复合物共免疫沉淀。雌激素诱导p72与hER α和TIF 2在细胞核中的共定位。p72/p68的存在增强了雌激素诱导的MCF 7细胞内源性pS2基因的表达。在瞬时表达试验中，p72/p68与SRA和一种TIF 2的组合对雌激素诱导的hER α反式激活产生了最终的协同作用。这些发现表明，p72/p68通过ER α AF-1作为ER亚型选择性辅激活因子，通过与辅激活因子复合物结合，通过与SRA和SRC-1/TIF 2家族蛋白直接结合来结合其AF-2。
One class of the nuclear receptor AF-2 coactivator complexes contains the SRC-1/TIF2 family, CBP/p300 and an RNA coactivator, SRA. We identified a subfamily of RNA-binding DEAD-box proteins (p72/p68) as a human estrogen receptor alpha (hER alpha) coactivator in the complex containing these factors. p72/p68 interacted with both the AD2 of any SRC-1/TIF2 family protein and the hER alpha A/B domain, but not with any other nuclear receptor tested. p72/p68, TIF2 (SRC-1) and SRA were co-immunoprecipitated with estrogen-bound hER alpha in MCF7 cells and in partially purified complexes associated with hER alpha from HeLa nuclear extracts. Estrogen induced co-localization of p72 with hER alpha and TIF2 in the nucleus. The presence of p72/p68 potentiated the estrogen-induced expression of the endogenous pS2 gene in MCF7 cells. In a transient expression assay, a combination of p72/p68 with SRA and one TIF2 brought an ultimate synergism to the estrogen-induced transactivation of hER alpha. These findings indicate that p72/p68 acts as an ER subtype-selective coactivator through ER alpha AF-1 by associating with the coactivator complex to bind its AF-2 through direct binding with SRA and the SRC-1/TIF2 family proteins.