RETINOIC ACID RECEPTORS INITIATE INDUCTION OF THE CYTOMEGALOVIRUS ENHANCER IN EMBRYONAL CELLS
RETINOIC ACID RECEPTORS INITIATE INDUCTION OF THE CYTOMEGALOVIRUS ENHANCER IN EMBRYONAL CELLS
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DOI：
10.1073/pnas.89.16.7630
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发表时间：
1992-08-15
影响因子：
11.1
通讯作者：
EVANS, RM
中科院分区：
文献类型：
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作者：
GHAZAL, P;DEMATTEI, C;EVANS, RM
潜伏病毒的再激活被认为是由信号转导事件引起的，该事件诱导了立即早期（IE）基因转录。有证据表明，人巨细胞病毒（hCMV）的主要IE启动子（MIEP）在人胚胎癌细胞中被生理水平的视黄酸（RA）激活。诱变实验定位于MIEP增强子，这是一种维甲酸反应元件，由河核苷酸分离的直接重复组成。蛋白质- dna结合实验表明，该元件作为RA核受体蛋白直接相互作用的特异性靶点。这些发现暗示维生素A （RA）的生物活性衍生物可能是婴儿和免疫功能低下成人hCMV发病机制的调节剂。
Reactivation of latent virus is believed to result from a signal transduction event that induces immediate-early (IE) gene transcription. Evidence is presented that the major IE promoter (MIEP) of human cytomegalovirus (hCMV) is activated by physiological levels of retinoic acid (RA) in human embryonal carcinoma cells. Mutagenesis experiments localized in the MIEP enhancer, a retinoic acid-responsive element composed of a direct repeat separated by rive nucleotides. Protein-DNA binding experiments revealed that this element functions as a specific target site for the direct interaction of nuclear receptor proteins for RA. These findings implicate the biologically active derivative of vitamin A (RA) as a potential modulator of hCMV pathogenesis in infants and immunocompromised adults.