Alternatively spliced isoforms of the human constitutive androstane receptor
Alternatively spliced isoforms of the human constitutive androstane receptor
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DOI：
10.1093/nar/gkg419
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发表时间：
2003-06-15
影响因子：
14.9
通讯作者：
Omiecinski, CJ
中科院分区：
文献类型：
--
作者：
Auerbach, SS;Ramsden, R;Omiecinski, CJ
核受体CAR （NR1I3）调节编码外源和类固醇代谢酶的基因的转录。由CAR介导的调节过程由一系列结构多样的化学物质（包括常见的药物和环境因子）调节。在这里，我们描述了人类CAR受体基因的四种帧内剪接变体。变异mRNA剪接转录物在所有被评估的人类肝脏中表达。剪接变异蛋白的分子模型预测，结构效应定位在受体的配体结合域内。评估功能的实验表明，与参考蛋白异构体相比，变异蛋白在DNA结合、转录激活和辅激活子募集方面表现出受损的活性。
The nuclear receptor CAR (NR1I3) regulates transcription of genes encoding xenobiotic- and steroid-metabolizing enzymes. Regulatory processes that are mediated by CAR are modulated by a structurally diverse array of chemicals including common pharmaceutical and environmental agents. Here we describe four in-frame splice variants of the human CAR receptor gene. The variant mRNA splice transcripts were expressed in all human livers evaluated. Molecular modeling of the splice variant proteins predicts that the structural effects are localized within the receptor's ligand-binding domain. Assays to assess function indicate that the variant proteins, when compared with the reference protein isoform, exhibit compromised activities with respect to DNA binding, transcriptional activation and coactivator recruitment.