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引用次数: 0
摘要
核视黄酸受体(RAR)是一种转录调节因子,以配体依赖的方式控制特定亚组基因的表达。开启同源靶基因转录的基本机制包括 RAR 与特定反应元件的结合,以及与核心调控蛋白复合物的相互作用网络。除了这种情况外,最近还出现了 N 端结构域和泛素-蛋白酶体系统的新作用。此外,RARs 的功能并不局限于调控同源靶基因,它们还能转抑其他基因通路。最后,RARs 还参与非基因组生物活动,如激活翻译和激酶级联。在此,我们将回顾这些机制,重点探讨激酶信号转导和蛋白酶体通路如何合作影响 RAR 转录活性的动态变化。
Dynamic and combinatorial control of gene expression by nuclear retinoic acid receptors (RARs).
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.