第二种人类视黄酸受体的鉴定。

Identification of a second human retinoic acid receptor.

作者信息

Brand N, Petkovich M, Krust A, Chambon P, de Thé H, Marchio A, Tiollais P, Dejean A

机构信息

Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Faculté de Médecine, Strasbourg, France.

出版信息

Nature. 1988 Apr 28;332(6167):850-3. doi: 10.1038/332850a0.

DOI:10.1038/332850a0

PMID:2833708

Abstract

We have previously described a human complementary DNA that encodes a novel protein which is homologous to members of the steroid/thyroid nuclear receptor multigene family. This novel protein (hap for hepatoma) exhibits strong homology with the human retinoic acid receptor (RAR) which has been recently characterized. To test the possibility that the hap protein might also be a retinoid receptor, a chimaeric receptor was created by replacing the putative DNA binding domain of hap with that of the human oestrogen receptor (ER). The resulting hap-ER chimaera was then tested for its ability to trans-activate an oestrogen-responsive reporter gene (vit-tk-CAT) in the presence of possible receptor ligands. Here we show that retinoic acid (RA) at physiological concentrations is effective in inducing the expression of this reporter gene by the hap-ER chimaeric receptor. This demonstrates the existence of two human retinoic acid receptors designated RAR-alpha and RAR-beta.

摘要

我们之前描述过一种人类互补DNA，它编码一种与类固醇/甲状腺核受体多基因家族成员同源的新型蛋白质。这种新型蛋白质（肝癌相关蛋白，hap）与最近已被鉴定的人类视黄酸受体（RAR）表现出很强的同源性。为了测试hap蛋白也可能是一种类维生素A受体的可能性，通过用人雌激素受体（ER）的假定DNA结合结构域替换hap的相应结构域，构建了一种嵌合受体。然后在存在可能的受体配体的情况下，测试所得的hap-ER嵌合体激活雌激素反应性报告基因（vit-tk-CAT）的能力。在此我们表明，生理浓度的视黄酸（RA）可有效地通过hap-ER嵌合受体诱导该报告基因的表达。这证明了存在两种人类视黄酸受体，分别命名为RAR-α和RAR-β。