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人类雄激素受体:互补脱氧核糖核酸克隆、序列分析及在前列腺中的基因表达

The human androgen receptor: complementary deoxyribonucleic acid cloning, sequence analysis and gene expression in prostate.

作者信息

Lubahn D B, Joseph D R, Sar M, Tan J, Higgs H N, Larson R E, French F S, Wilson E M

机构信息

Laboratories for Reproductive Biology, University of North Carolina, Chapel Hill 27599.

出版信息

Mol Endocrinol. 1988 Dec;2(12):1265-75. doi: 10.1210/mend-2-12-1265.

DOI:10.1210/mend-2-12-1265
PMID:3216866
Abstract

Androgenic hormones mediate their effects on male sex differentiation and development through a high affinity receptor protein. We report here cloning of the complete coding sequence of the human androgen receptor (hAR). By sequence homology hAR is a member of the nuclear receptor family, with closest sequence identity to the progesterone, mineralocorticoid, and glucocorticoid receptors. Regions of highest homology include the DNA-binding domain and a small region within the hydrophobic ligand-binding domain. Comparison of the deduced 919 amino acid sequence of hAR (98,999 mol wt) to the 902 amino acid sequence of rat AR (98,227 mol wt) reveals identical sequences in the DNA- and hormone-binding domains, with an overall homology of 85%. In human prostate, the major androgen receptor mRNA species is 10 kilobases while a less abundant mRNA is approximately 7 kilobases. Rabbit polyclonal antibodies were raised against a synthetic peptide from the N-terminal region of hAR. Immunocytochemical analysis of human prostate tissue demonstrated that AR is localized predominantly in nuclei of glandular epithelial cells.

摘要

雄激素通过一种高亲和力受体蛋白介导其对男性性别分化和发育的作用。我们在此报告人类雄激素受体(hAR)完整编码序列的克隆。通过序列同源性分析,hAR是核受体家族的成员,与孕酮、盐皮质激素和糖皮质激素受体的序列同一性最高。同源性最高的区域包括DNA结合结构域和疏水配体结合结构域内的一个小区域。将推导的hAR 919个氨基酸序列(98,999道尔顿分子量)与大鼠AR的902个氨基酸序列(98,227道尔顿分子量)进行比较,发现DNA和激素结合结构域中的序列相同,总体同源性为85%。在人类前列腺中,主要的雄激素受体mRNA种类为10千碱基,而较少丰度的mRNA约为7千碱基。针对hAR N端区域的合成肽制备了兔多克隆抗体。对人类前列腺组织的免疫细胞化学分析表明,AR主要定位于腺上皮细胞核中。

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The human androgen receptor: complementary deoxyribonucleic acid cloning, sequence analysis and gene expression in prostate.人类雄激素受体:互补脱氧核糖核酸克隆、序列分析及在前列腺中的基因表达
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Specific region in hormone binding domain is essential for hormone binding and trans-activation by human androgen receptor.激素结合域中的特定区域对于人雄激素受体的激素结合和反式激活至关重要。
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A frameshift mutation destabilizes androgen receptor messenger RNA in the Tfm mouse.移码突变使Tfm小鼠中的雄激素受体信使核糖核酸不稳定。
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Mol Endocrinol. 1993 Jul;7(7):861-9. doi: 10.1210/mend.7.7.8413310.

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