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NR4A orphan nuclear receptors in cardiovascular biology

机译:NR4A孤儿核受体在心血管生物学中的作用

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The NR4A orphan nuclear receptor subfamily comprises the highly homologous receptors Nur77 (NR4A1), Nurr1 (NR4A2) and NOR1 (NR4A3). These evolutionarily conserved and ancient receptors function as ligand-independent transcription factors that regulate the expression of overlapping target genes. As early response genes, the basal expression level of these receptors is low but rapidly induced as a result of the changes in environmental cues. The transcrip-tional activity of these receptors is primarily regulated by gene induction and posttranslational modifications of the receptor including phosphorylation. NR4A receptors were initially identified in the brain and early functional studies suggested a role for these receptors in signal- and cell-specific stimulation of both apoptosis and proliferation. More recent studies have revealed much broader functions of these orphan receptors including the regulation of genes involved in cancer, metabolism, energy balance, atherosclerosis and vascular remodeling. In this review, we will discuss our current understanding of the molecular biology of NR4A receptors and summarize recent studies suggesting an important role of these orphan receptors in vascular biology.
机译:NR4A孤儿核受体亚家族包含高度同源的受体Nur77(NR4A1),Nurr1(NR4A2)和NOR1(NR4A3)。这些在进化上保守和古老的受体起着独立于配体的转录因子的作用,调节重叠靶基因的表达。作为早期响应基因,这些受体的基础表达水平较低,但由于环境提示的变化而被迅速诱导。这些受体的转录活性主要受基因诱导和受体的翻译后修饰(包括磷酸化)调节。 NR4A受体最初是在大脑中发现的,早期的功能研究表明这些受体在凋亡和增殖的信号和细胞特异性刺激中起着作用。最近的研究表明这些孤儿受体具有更广泛的功能,包括调节与癌症,代谢,能量平衡,动脉粥样硬化和血管重塑有关的基因。在这篇综述中,我们将讨论我们对NR4A受体分子生物学的当前理解,并总结最近的研究,这些研究提示这些孤儿受体在血管生物学中的重要作用。

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