A third human retinoic acid receptor, hRAR-gamma.
A third human retinoic acid receptor, hRAR-gamma.
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第三种人类视黄酸受体，hRAR-γ。
DOI：
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发表时间：
1989
影响因子：
11.1
通讯作者：
P. Chambon
中科院分区：
文献类型：
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作者：
A. Krust;P. Kastner;M. Petkovich;A. Zelent;P. Chambon
视黄酸受体（RARs）是维甲酸（RA）诱导增强因子，属于类固醇/甲状腺核受体超家族。我们之前已经鉴定了两种人类RAR (har - α和har - β) cdna，并且最近克隆了它们的小鼠同源物（mrar - α和mrar - β）以及第三种RAR (mrar - γ)，其RNA主要在皮肤中检测到，这是众所周知的RA靶点。本文利用mRAR-gamma cDNA从一个T47D乳腺癌细胞cDNA文库中克隆其人类对应物（hRAR-gamma）。通过在HeLa细胞中的瞬时转染实验和含有合成RA反应元件的报告基因，我们证明了hra - γ cDNA确实编码RA诱导的转录反式激活子。有趣的是，对所有六种人类和小鼠RARs的氨基酸序列的比较表明，RAR亚家族中特定成员（α、β或γ）的种间保守性远远高于所有三种受体在给定物种中的保守性。这些观察结果表明，rar - α、- β和- γ可能具有特定的功能。我们还表明，hrar - γ RNA是人类皮肤中主要的RAR RNA种类，这表明hrar - γ介导了该组织中的一些类视黄醛效应。
Retinoic acid receptors (RARs) are retinoic acid (RA)-inducible enhancer factors belonging to the superfamily of steroid/thyroid nuclear receptors. We have previously characterized two human RAR (hRAR-alpha and hRAR-beta) cDNAs and have recently cloned their murine cognates (mRAR-alpha and mRAR-beta) together with a third RAR (mRAR-gamma) whose RNA was detected predominantly in skin, a well-known target for RA. mRAR-gamma cDNA was used here to clone its human counterpart (hRAR-gamma) from a T47D breast cancer cell cDNA library. Using a transient transfection assay in HeLa cells and a reporter gene harboring a synthetic RA responsive element, we demonstrate that hRAR-gamma cDNA indeed encodes a RA-inducible transcriptional trans-activator. Interestingly, comparisons of the amino acid sequences of all six human and mouse RARs indicate that the interspecies conservation of a given member of the RAR subfamily (either alpha, beta, or gamma) is much higher than the conservation of all three receptors within a given species. These observations indicate that RAR-alpha, -beta, and -gamma may perform specific functions. We show also that hRAR-gamma RNA is the predominant RAR RNA species in human skin, which suggests that hRAR-gamma mediates some of the retinoid effects in this tissue.