Human ERRγ, a third member of the estrogen receptor-related receptor (ERR) subfamily of orphan nuclear receptors: Tissue-specific isoforms are expressed during development and in the adult
Human ERRγ, a third member of the estrogen receptor-related receptor (ERR) subfamily of orphan nuclear receptors: Tissue-specific isoforms are expressed during development and in the adult
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DOI：
10.1210/me.14.3.382
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发表时间：
2000-03-01
影响因子：
--
通讯作者：
Vissing, H
中科院分区：
文献类型：
--
作者：
Heard, DJ;Norby, PL;Vissing, H
核受体蛋白超家族是高等真核生物中一大类转录因子，参与动物发育、组织分化和体内平衡的许多方面。受体的一个亚家族，ERR α和β（雌激素受体相关受体α和β），与ER密切相关，是第一批被鉴定的孤儿核受体。这些受体可以结合DNA作为单体，并被认为是组成性激活转录，不受β-雌二醇的影响。对ERR α表达模式的研究和ERR β的基因破坏实验表明，它们在小鼠特定组织的发育和分化中起重要作用。在这项工作中，我们证明了在人类中存在的第三个成员，这个亚家族的受体，称为ERR γ，这是高度表达在许多不同的胎儿和成人组织，包括脑，肾，胰腺和胎盘。ERR γ mRNA在5 '端高度选择性剪接，产生许多组织特异性RNA种类，其中一些编码N-末端区域不同的蛋白质同种型。与ERR α和β一样，ERR γ作为单体与埃雷结合。GAL 4-ERR γ融合蛋白在转染的HEK 293细胞中以配体非依赖性方式激活转录的程度大于GAL-4 ERR α或-β融合蛋白。
The nuclear receptor protein superfamily is a large group of transcription factors involved in many aspects of animal development, tissue differentiation, and homeostasis in the higher eukaryotes. A subfamily of receptors, ERR alpha and beta (estrogen receptor-related receptor alpha and beta), closely related to the ER, were among the first orphan nuclear receptors identified. These receptors can bind DNA as monomers and are thought to activate transcription constitutively, unaffected by beta-estradiol. Studies of the expression patterns of ERR alpha and gene disruption experiments of ERR beta indicate that they play an important role in the development and differentiation of specific tissues in the mouse. In this work we demonstrate the existence in humans of a third member of this subfamily of receptors, termed ERR gamma, which is highly expressed in a number of diverse fetal and adult tissues including brain, kidney, pancreas, and placenta. The ERR gamma mRNA is highly alternatively spliced at the 5'-end, giving rise to a number of tissue-specific RNA species, some of which code for protein isoforms differing in the N-terminal region. Like ERR alpha and beta, ERR gamma binds as a monomer to an ERRE. A GAL4-ERR gamma fusion protein activates transcription in a ligand-independent manner in transfected HEK293 cells to a greater degree than either the GAL-4ERR alpha or -beta fusion proteins.