人雌激素受体α（hERα）与鸡卵清蛋白上游启动子转录因子I（COUP-TFI）复合物的形成通过丝裂原活化蛋白激酶（MAPK）介导的Ser118磷酸化增强hERα的激活功能1（AF-1）。
Formation of an hER alpha-COUP-TFI complex enhances hER alpha AF-1 through Ser118 phosphorylation by MAPK.
作者信息
Métivier Raphaël, Gay Frédérique A, Hübner Michael R, Flouriot Gilles, Salbert Gilles, Gannon Frank, Kah Olivier, Pakdel Farzad
机构信息
Equipe d'Endocrinologie Moléculaire de la Reproduction, UMR CNRS 6026, Université de Rennes I, 35042 Rennes Cedex, France.
出版信息
EMBO J. 2002 Jul 1;21(13):3443-53. doi: 10.1093/emboj/cdf344.
Abstract
The enhancement of the human estrogen receptor alpha (hER alpha, NR3A1) activity by the orphan nuclear receptor COUP-TFI is found to depend on the establishment of a tight hER alpha-COUP-TFI complex. Formation of this complex seems to involve dynamic mechanisms different from those allowing hER alpha homodimerization. Although the hER alpha-COUP-TFI complex is present in all cells tested, the transcriptional cooperation between the two nuclear receptors is restricted to cell lines permissive to hER alpha activation function 1 (AF-1). In these cells, the physical interaction between COUP-TFI and hER alpha increases the affinity of hER alpha for ERK2/p42(MAPK), resulting in an enhanced phosphorylation state of the hER alpha Ser118. hER alpha thus acquires a strengthened AF-1 activity due to its hyperphosphorylation. These data indicate an alternative interaction process between nuclear receptors and demonstrate a novel protein intercommunication pathway that modulates hER alpha AF-1.
摘要
研究发现，孤儿核受体COUP-TFI对人雌激素受体α（hERα，NR3A1）活性的增强作用依赖于紧密的hERα-COUP-TFI复合物的形成。该复合物的形成似乎涉及与hERα同二聚化不同的动态机制。尽管hERα-COUP-TFI复合物存在于所有测试细胞中，但这两种核受体之间的转录协同作用仅限于允许hERα激活功能1（AF-1）的细胞系。在这些细胞中，COUP-TFI与hERα之间的物理相互作用增加了hERα对ERK2/p42（MAPK）的亲和力，导致hERα Ser118的磷酸化状态增强。由于hERα的过度磷酸化，其AF-1活性因此增强。这些数据表明了核受体之间的另一种相互作用过程，并证明了一种调节hERα AF-1的新型蛋白质相互交流途径。
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本文引用的文献
1
Minireview: genomic organization of the human ERalpha gene promoter region.小型综述：人类雌激素受体α基因启动子区域的基因组组织
Mol Endocrinol. 2001 Dec;15(12):2057-63. doi: 10.1210/mend.15.12.0731.
2
Synergism between ERalpha transactivation function 1 (AF-1) and AF-2 mediated by steroid receptor coactivator protein-1: requirement for the AF-1 alpha-helical core and for a direct interaction between the N- and C-terminal domains.类固醇受体辅激活蛋白-1介导的雌激素受体α反式激活功能1（AF-1）与AF-2之间的协同作用：对AF-1α螺旋核心以及N端和C端结构域之间直接相互作用的需求。
Mol Endocrinol. 2001 Nov;15(11):1953-70. doi: 10.1210/mend.15.11.0727.
3
Mechanisms of estrogen action.雌激素的作用机制。
Physiol Rev. 2001 Oct;81(4):1535-65. doi: 10.1152/physrev.2001.81.4.1535.
4
Estrogens and health in males.雌激素与男性健康。
Mol Cell Endocrinol. 2001 Jun 10;178(1-2):51-5. doi: 10.1016/s0303-7207(01)00420-8.
5
Increase in the stability and helical content of estrogen receptor alpha in the presence of the estrogen response element: analysis by circular dichroism spectroscopy.在雌激素反应元件存在的情况下雌激素受体α的稳定性和螺旋含量增加：圆二色光谱分析
Biochemistry. 2001 Jun 5;40(22):6646-52. doi: 10.1021/bi002846l.
6
COUP-TFI (chicken ovalbumin upstream promoter-transcription factor I) regulates cell migration and axogenesis in differentiating P19 embryonal carcinoma cells.COUP-TFI（鸡卵清蛋白上游启动子转录因子I）调节分化中的P19胚胎癌细胞的细胞迁移和轴突发生。
Mol Endocrinol. 2000 Dec;14(12):1918-33. doi: 10.1210/mend.14.12.0562.
7
Identification of a new isoform of the human estrogen receptor-alpha (hER-alpha) that is encoded by distinct transcripts and that is able to repress hER-alpha activation function 1.鉴定出一种人类雌激素受体α（hER-α）的新亚型，它由不同的转录本编码，并且能够抑制hER-α激活功能1。
EMBO J. 2000 Sep 1;19(17):4688-700. doi: 10.1093/emboj/19.17.4688.
8
9
Identification of an estrogen-mediated deoxyribonucleic acid-binding independent transactivation pathway on the epidermal growth factor receptor gene promoter.表皮生长因子受体基因启动子上雌激素介导的不依赖脱氧核糖核酸结合的反式激活途径的鉴定。
Endocrinology. 2000 Jun;141(6):2266-74. doi: 10.1210/endo.141.6.7521.
10
p300 mediates functional synergism between AF-1 and AF-2 of estrogen receptor alpha and beta by interacting directly with the N-terminal A/B domains.p300 通过直接与 N 端 A/B 结构域相互作用，介导雌激素受体α和β的 AF-1 与 AF-2 之间的功能协同作用。
J Biol Chem. 2000 May 26;275(21):15645-51. doi: 10.1074/jbc.M000042200.
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