Auerbach Scott S, Ramsden Richard, Stoner Matthew A, Verlinde Christophe, Hassett Christopher, Omiecinski Curtis J
Department of Pharmacology, University of Washington, Seattle, WA, USA.
Nucleic Acids Res. 2003 Jun 15;31(12):3194-207. doi: 10.1093/nar/gkg419.
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.
核受体CAR（NR1I3）调控编码异生素和类固醇代谢酶的基因的转录。由CAR介导的调控过程受到结构多样的一系列化学物质的调节，这些化学物质包括常见的药物和环境因子。在此，我们描述了人类CAR受体基因的四种读码框内剪接变体。这些变体mRNA剪接转录本在所有评估的人类肝脏中均有表达。对剪接变体蛋白的分子建模预测，结构效应定位于受体的配体结合域内。评估功能的试验表明，与参考蛋白异构体相比，这些变体蛋白在DNA结合、转录激活和共激活因子募集方面的活性受损。
