Homologous down regulation of the glucocorticoid receptor: the molecular machinery.
Homologous down regulation of the glucocorticoid receptor: the molecular machinery.
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DOI：
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发表时间：
1993
影响因子：
1.6
通讯作者：
Oakley Rh;Cidlowski Ja
中科院分区：
文献类型：
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作者：
Oakley Rh;Cidlowski Ja
摘要糖皮质激素的生物学作用是由细胞内糖皮质激素受体(GR)介导的，当GR被同源配体结合时，作为DNA结合蛋白，增强或抑制反应基因的基础转录速率。细胞对糖皮质激素的敏感性与受体浓度成正比。在大多数细胞中，糖皮质激素通过称为同源下调的过程促进GR水平的降低。因此，这种配体诱导、受体介导的事件限制了细胞对糖皮质激素的反应范围。在过去的十年里，GR下调调控的分子机制一直是许多报道的主题。这些研究的共识是，GR基因转录减少和翻译后受体周转增加都是导致受体浓度降低的原因。对于是否也涉及GR mRNA稳定性的转录后改变，人们的共识相当少。目前GR下调研究的重点是确定受体基因中对GR mRNA合成减少至关重要的顺式元件，并确定其他信号转导途径在调节脱敏过程中所起的作用。
Abstract The biological action of glucocorticoids is mediated by intracellular glucocorticoid receptors (GR) that, when bound by homologous ligand, function as DNA-binding proteins that enhance or repress basal transcription rates of responsive genes. The cellular sensitivity to glucocorticoids is directly proportional to the receptor concentration. In most cells, glucocorticoids promote a reduction in GR levels by a process termed homologous down regulation. This ligand-induced, receptor-mediated event consequently limits the span of cellular responsiveness to glucocorticoids. In the last decade, the molecular mechanisms underlying GR down regulation have been the subject of many reports. The consensus of these studies is that both a decrease in transcription of the GR gene and a posttranslational increase in receptor turnover contribute to the reduction in receptor concentration. There is considerably less agreement as to whether a posttranscriptional alteration in GR mRNA stability is also involved. The current thrust of GR down regulation research seeks to identify cis-elements within the receptor gene that are crucial for the decrease in GR mRNA synthesis and to determine the role, if any, other signal transduction pathways play in modulating the desensitizing process.