Suppression of estrogen receptor transcriptional activity by connective tissue growth factor.
Suppression of estrogen receptor transcriptional activity by connective tissue growth factor.
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结缔组织生长因子抑制雌激素受体转录活性
DOI：
10.1371/journal.pone.0020028
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Ye Q
中科院分区：
文献类型：
--
作者：
Cheng L;Yang Z;Wang X;Jiao Y;Xie X;Lin J;Zhang H;Han J;Jiang K;Ye Q
已显示分泌的生长因子刺激负责许多生物过程的雌激素受体（ER）的转录活性。然而，这些生长因子是否与ER发生物理相互作用仍不清楚。在这里，我们首次表明，结缔组织生长因子（CTGF）的物理和功能与ER。CTGF与ER在体内外均存在相互作用。CTGF与ER DNA结合域相互作用。CTGF中的ER相互作用区域被映射到血小板反应蛋白I型重复序列，一种细胞附着基序。CTGF的过表达抑制ER的转录活性以及雌激素反应基因的表达，包括pS2和组织蛋白酶D。用CTGF小干扰RNA减少内源性CTGF增强ER转录活性。CTGF和ER之间的相互作用是CTGF抑制雌激素应答性转录所必需的。此外，CTGF降低ER蛋白表达，而CTGF突变体，不抑制ER转录活性也没有改变ER蛋白水平。这些结果提示CTGF和ER之间的相互作用可能是雌激素信号转导的转录调控机制，从而为分泌型生长因子和ER信号通路之间的相互作用提供了一种新的机制。
Secreted growth factors have been shown to stimulate the transcriptional activity of estrogen receptors (ER) that are responsible for many biological processes. However, whether these growth factors physically interact with ER remains unclear. Here, we show for the first time that connective tissue growth factor (CTGF) physically and functionally associates with ER. CTGF interacted with ER both in vitro and in vivo. CTGF interacted with ER DNA-binding domain. ER interaction region in CTGF was mapped to the thrombospondin type I repeat, a cell attachment motif. Overexpression of CTGF inhibited ER transcriptional activity as well as the expression of estrogen-responsive genes, including pS2 and cathepsin D. Reduction of endogenous CTGF with CTGF small interfering RNA enhanced ER transcriptional activity. The interaction between CTGF and ER is required for the repression of estrogen-responsive transcription by CTGF. Moreover, CTGF reduced ER protein expression, whereas the CTGF mutant that did not repress ER transcriptional activity also did not alter ER protein levels. The results suggested the transcriptional regulation of estrogen signaling through interaction between CTGF and ER, and thus may provide a novel mechanism by which cross-talk between secreted growth factor and ER signaling pathways occurs.
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影响因子：
7.5
作者：
Lichtner, RB
通讯作者：
Lichtner, RB
影响因子：
10.3
作者：
Chang, Cheng-Chi;Lin, Ming-Tsai;Kuo, Min-Liang
通讯作者：
Kuo, Min-Liang
影响因子：
--
作者：
Hou, XN;Tan, Y;Das, SK
通讯作者：
Das, SK
DOI：
10.1073/pnas.0809516106
发表时间：
2009-03-10
影响因子：
11.1
作者：
Ford, Caroline E.;Ekstrom, Elin J.;Andersson, Tommy
通讯作者：
Andersson, Tommy
影响因子：
4.8
作者：
Hishikawa, K;Oemar, BS;Fujii, T
通讯作者：
Fujii, T