GAS, a new glutamate-rich protein, interacts differentially with SRCs and is involved in oestrogen receptor function

GAS, a new glutamate-rich protein, interacts differentially with SRCs and is involved in oestrogen receptor function
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GAS 是一种新的富含谷氨酸的蛋白质,与 SRC 存在不同的相互作用,并参与雌激素受体功能

DOI:
10.1038/embor.2008.223
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发表时间:
2009-01-01
期刊:
影响因子:
7.7
通讯作者:
Shang, Yongfeng
Shang, Yongfeng
中科院分区:
生物学2区
文献类型:
--
作者:
Liang, Jing;Zhang, Hua;Shang, Yongfeng

文献摘要

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类固醇受体辅激活因子(SRCs)对动物的发育和生理有着重要的影响。遗传消融实验表明,各种SRC蛋白可能具有不同的生理作用,然而,功能特异性的明确证据尚未在分子水平上显示。在这里,我们报告了一个新的SRC 1相互作用蛋白,谷氨酸丰富的辅激活因子与SRC 1(GAS),其中包含一个中央谷氨酸丰富的区域,并具有反式激活活性的相互作用。有趣的是,GAS仅与SRC 1相互作用,而不与糖皮质激素受体相互作用蛋白1(GRIP 1)或在乳腺癌中扩增的蛋白1(AIB 1)相互作用,这是SRC家族的另外两个成员。它与雌激素受体α(ER α)相互作用,参与雌激素受体调节的基因转录和雌激素刺激的G1/S细胞周期转换。因此,我们的数据表明,GAS是一种新的转录辅因子,不同的SRC与不同的二级辅因子。
Steroid receptor coactivators (SRCs) exert profound effects on animal development and physiology. Genetic ablation experiments indicate that various SRC proteins might have differential physiological roles; however, clear evidence of functional specificity has not yet been shown at the molecular level. Here we report the identification of a new SRC1 interacting protein, glutamate-rich coactivator interacting with SRC1 (GAS), which contains a central glutamate-rich region and has transactivation activity. Interestingly, GAS interacts only with SRC1, and not with glucocorticoid receptor interacting protein 1 (GRIP1) or amplified in breast cancer 1 (AIB1), the other two members of the SRC family. It interacts with oestrogen receptor-alpha (ER alpha) and participates in both oestrogen receptor-regulated gene transcription and oestrogen-stimulated G1/S cell-cycle transition. Our data thus indicate that GAS is a new transcription cofactor and that different SRCs are associated with distinct secondary cofactors.