Comparing the rules of engagement of androgen and glucocorticoid receptors.
Comparing the rules of engagement of androgen and glucocorticoid receptors.
复制标题
DOI：
10.1007/s00018-017-2467-3
复制
发表时间：
2017-06
期刊：
影响因子：
--
通讯作者：
Helsen C
中科院分区：
文献类型：
--
作者：
Claessens F;Joniau S;Helsen C
尽管雄激素和糖皮质激素具有不同的生理活性，但相应的受体是核受体超家族的非常接近的成员。它们的作用机制显示出惊人的相似性，因为两种受体识别非常相似的DNA反应元件，并将相同的共激活因子招募到它们的靶基因。反应的特异性主要在于受体的组织特异性表达及其配体特异性。在两种受体都表达的细胞中，导致靶基因差异的机制不太明显。它们部分在于DNA结合位点的细微变化，与其他转录因子的协同性以及从DNA和配体到其他受体结构域的差异变构信号。我们将强调可能解释DNA序列选择性的不同建议，并将比较反应元件和反式激活过程中不同功能之间可能的变构途径。雄激素和糖皮质激素受体的相互作用在临床环境中也高度相关，其中两种受体都是治疗靶向的。我们将讨论糖皮质激素和雄激素受体在去势抵抗性前列腺癌中发挥部分冗余作用的可能性。
Despite the diverse physiological activities of androgens and glucocorticoids, the corresponding receptors are very close members of the nuclear-receptor super family. Their action mechanisms show striking similarities, since both receptors recognize very similar DNA-response elements and recruit the same coactivators to their target genes. The specificity of the responses lies mainly in the tissue-specific expression of the receptors and in their ligand specificity. In cells, where both receptors are expressed, the mechanisms leading to the difference in target genes are less obvious. They lie in part in subtle variations of the DNA-binding sites, in cooperativity with other transcription factors and in differential allosteric signals from the DNA and ligand to other receptor domains. We will highlight the different suggestions that might explain the DNA sequence selectivity and will compare the possible allosteric routes between the response elements and the different functions in the transactivation process. The interplay of androgen and glucocorticoid receptors is also highly relevant in clinical settings, where both receptors are therapeutically targeted. We will discuss the possibility that the glucocorticoid and androgen receptors can play partially redundant roles in castration-resistant prostate cancer.