p300 is a component of an estrogen receptor coactivator complex

p300 is a component of an estrogen receptor coactivator complex
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DOI:
10.1073/pnas.93.21.11540
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发表时间:
1996-10-15
影响因子:
11.1
通讯作者:
Brown, M
Brown, M
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Hanstein, B;Eckner, R;Brown, M

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雌激素受体(ER)是一种配体依赖的转录因子,它与其他细胞信号通路一起调节靶基因的表达,以响应雌激素。这表明内质网将激活信号传递给一般转录机制的机制可能包括整合这些不同信号的因素。我们之前已经描述了雌激素受体相关蛋白ERAP160,作为一种以激动剂依赖的方式与ER复合物的因子。我们现在已经发现转录辅激活因子p300与激动剂结合的内质网结合,并增强内质网对配体依赖性的激活。我们的研究表明,内质网共激活因子复合物涉及内质网和ERAP160之间的直接激素依赖性相互作用,导致p300的募集。此外,针对克隆的类固醇受体共激活因子1 (SRC1)的抗体可以识别ERAP160。已知p300在多种信号转导通路中的作用,包括那些涉及第二信使cAMP的信号转导通路,表明p300是内质网和这些其他通路之间的一个整合点。
The estrogen receptor (ER) is a ligand-dependent transcription factor that regulates expression of target genes in response to estrogen in concert with other cellular signaling pathways. This suggests that the mechanism by which ER transmits an activating signal to the general transcription machinery may include factors that integrate these diverse signals. We have previously characterized the estrogen receptor-associated protein, ERAP160, as a factor that complexes with ER in an agonist-dependent manner. We have now found that the transcriptional coactivator p300 associates with agonist bound ER and augments ligand-dependent activation by ER. Our studies show that an ER coactivator complex involves a direct hormone-dependent interaction between ER and ERAP160, resulting in the recruitment of p300. In addition, antibodies directed against the cloned steroid receptor coactivator 1 (SRC1) recognize ERAP160. The known role of p300 in multiple signal transduction pathways, including those involving the second messenger cAMP, suggests p300 functions as a point of integration between ER and these other pathways.