Dynamic and combinatorial control of gene expression by nuclear retinoic acid receptors (RARs).
Dynamic and combinatorial control of gene expression by nuclear retinoic acid receptors (RARs).
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DOI：
10.1621/nrs.07005
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发表时间：
2009-05-08
期刊：
影响因子：
--
通讯作者：
Germain P
中科院分区：
文献类型：
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作者：
Rochette-Egly C;Germain P
核视黄酸受体（RAR）是转录调节因子，以配体依赖性方式控制特定基因子集的表达。开启同源靶基因转录的基本机制涉及 RAR 在特定反应元件上的结合以及与共调节蛋白复合物的相互作用网络，其组装由 RAR 的 C 端配体结合结构域指导。除了这种情况之外，N 末端结构域和泛素蛋白酶体系统的新作用最近也出现了。此外，RAR 的功能不仅限于调节同源靶基因，因为它们还可以反式抑制其他基因途径。最后，RAR 还参与非基因组生物活性，例如翻译和激酶级联的激活。在这里，我们将回顾这些机制，重点关注激酶信号传导和蛋白酶体途径如何合作影响 RAR 转录活性的动态。
Nuclear retinoic acid receptors (RARs) are transcriptional regulators controlling the expression of specific subsets of genes in a ligand-dependent manner. The basic mechanism for switching on transcription of cognate target genes involves RAR binding at specific response elements and a network of interactions with coregulatory protein complexes, the assembly of which is directed by the C-terminal ligand-binding domain of RARs. In addition to this scenario, new roles for the N-terminal domain and the ubiquitin-proteasome system recently emerged. Moreover, the functions of RARs are not limited to the regulation of cognate target genes, as they can transrepress other gene pathways. Finally, RARs are also involved in nongenomic biological activities such as the activation of translation and of kinase cascades. Here we will review these mechanisms, focusing on how kinase signaling and the proteasome pathway cooperate to influence the dynamics of RAR transcriptional activity.