The mouse estrogen receptor-related orphan receptor alpha 1: molecular cloning and estrogen responsiveness.

The mouse estrogen receptor-related orphan receptor alpha 1: molecular cloning and estrogen responsiveness.
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小鼠雌激素受体相关孤儿受体α1:分子克隆和雌激素反应性。

DOI:
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发表时间:
1997
影响因子:
3.5
通讯作者:
C. Teng
C. Teng
中科院分区:
医学3区
文献类型:
--
作者:
H. Shigeta;W. Zuo;N. Yang;R. Diaugustine;C. Teng

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雌激素受体相关孤儿受体α1是类固醇/甲状腺核受体超家族的成员。我们已经克隆了人雌激素受体相关孤儿受体α1(HERRα1)的cDNA,并证明它能增强乳铁蛋白基因启动子在转染人子宫内膜癌细胞中的雌激素反应性。在本研究中,我们以Herrα1为探针,从脑和肾脏的cDNA文库中分离出小鼠Errα1的同源物。人和小鼠ERRα1的序列比较表明,其核苷酸同源性为%,氨基酸同源性为97%。通过凝胶迁移率改变分析,我们证明谷胱甘肽S-转移酶-Merrα1融合蛋白是在细菌系统中产生的,与人Errα1DNA结合元件结合。小鼠子宫核提取物也与该DNA元件相互作用,在迁移率改变分析中产生了三个复合体,其中一个被Herrα1抗血清超位。Northern分析在所有受试的成年小鼠组织中都检测到2.2kbp的转录本;然而,在这些组织中发现ERRα1mRNA的量存在很大的差异。Western分析在非生殖组织中检测到多种免疫反应形式的小鼠ERRα1,而在生殖组织中发现主要的53 kDa蛋白,如子宫、宫颈和阴道。己烯雌酚(DES)刺激19日龄小鼠子宫ERRα1mRNA的表达。我们发现,DES和雌二醇,而不是黄体酮或地塞米松,提高了小鼠子宫中免疫反应ERRα1的水平。这些结果表明,ERRα1是小鼠子宫中的雌激素反应基因,并为研究这种核孤儿受体的生物学作用提供了一个模型系统。
Estrogen receptor-related orphan receptor alpha 1 is a member of the steroid/thyroid nuclear receptor superfamily. We have previously cloned the human estrogen receptor-related orphan receptor alpha 1 (hERR alpha 1) cDNA and demonstrated that it enhances estrogen responsiveness of the lactoferrin gene promoter in transfected human endometrial carcinoma cells. In the present study, we used the hERR alpha 1 cDNA as a probe and isolated the mouse homologue of ERR alpha 1 from the cDNA libraries of the brain and kidney. Sequence comparison between human and mouse ERR alpha 1 (mERR alpha 1) revealed that the homologies are 89% in nucleotides and 97% in amino acids. By electrophoresis mobility shift assay, we showed that the glutathione S-transferase-mERR alpha 1 fusion protein produced in a bacterial system bound to the human ERR alpha 1 DNA-binding element. Mouse uterine nuclear extract also interacted with this DNA element and produced three complexes in the mobility shift assay, one of which was supershifted by the hERR alpha 1 antiserum. A 2.2 kbp transcript was detected by Northern analysis in all adult mouse tissues tested; however, large variations in the amount of ERR alpha 1 mRNA were found among them. Multiple immunoreactive forms of mouse ERR alpha 1 were detected by Western analysis in non-reproductive tissues, whereas a major 53 kDa protein was found in reproductive tissues such as uterus, cervix and vagina. Diethylstilbestrol (DES) stimulated the expression of ERR alpha 1 mRNA in the uterus of 19-day-old mouse. We showed that DES and estradiol, but not progesterone or dexamethasone, enhanced the level of immunoreactive ERR alpha 1 in the mouse uterus. These results demonstrated that the ERR alpha 1 is an estrogen-responsive gene in the mouse uterus and provides a model system with which to study the biological roles of this nuclear orphan receptor.
DOI: 10.1016/s0021-9258(17)40767-8
发表时间: 1994-06
期刊: The Journal of biological chemistry
影响因子: --
作者:
V. Krishnan;Xiahong Wang;S. Safe
通讯作者: V. Krishnan;Xiahong Wang;S. Safe
DOI: 10.1210/mend.7.5.7686253
发表时间: 1993-05
影响因子: --
作者:
Patrick F. Sullivan;Yan-min Wang;D. R. Joseph
通讯作者: Patrick F. Sullivan;Yan-min Wang;D. R. Joseph
DOI: 10.1002/j.1460-2075.1991.tb07922.x
发表时间: 1991-01-01
期刊: EMBO JOURNAL
影响因子: 11.4
作者:
ZELENT, A;MENDELSOHN, C;CHAMBON, P
通讯作者: CHAMBON, P