Kato S
Institute of Molecular and Cellular Biosciences, University of Tokyo.
Nihon Rinsho. 1998 Jul;56(7):1699-704.
Nuclear receptors for steroid/thyroid hormones, vitamin A,D and fat-soluble ligands form a gene superfamily of ligand-inducible transcription factors, which plays an important roles in a wide spectrum of biological events by regulating expression of a set of target genes. Two domains (A/B and E) of nuclear receptors are demonstrated to activate transcription, designated AF-1 (A/B) and AF-2 (E), respectively. Homo- and hetero-dimers of nuclear receptors bind target enhancer elements in the target gene promoters. The target enhancer elements are referred as hormone response elements (HRE), and composed of two hexamer core motifs. The orientations and spaces between two core motifs play critical roles in discreminating the recognition of HREs among the members of nuclear receptor. DNA-bound nuclear receptors controls transcription in a ligand-binding dependent way in co-operation with a multiprotein complex containing RNA polymerase II and a series of auxiliary factors, TFIIA,B,D, E,F and H. During process of ligand-induced transactivation by nuclear receptors, nuclear co-factors interacting with the AF-1 and AF-2 seem to be involved. Several transcriptional co-activators and co-repressors have been recently identified, and their function is currently under investigation.
类固醇/甲状腺激素、维生素A、D及脂溶性配体的核受体形成了一个配体诱导型转录因子的基因超家族,该家族通过调控一组靶基因的表达,在广泛的生物学事件中发挥重要作用。核受体的两个结构域(A/B和E)被证明可激活转录,分别命名为AF-1(A/B)和AF-2(E)。核受体的同二聚体和异二聚体与靶基因启动子中的靶增强子元件结合。这些靶增强子元件被称为激素反应元件(HRE),由两个六聚体核心基序组成。两个核心基序之间的方向和间距在区分核受体成员对HRE的识别中起关键作用。与DNA结合的核受体与包含RNA聚合酶II和一系列辅助因子TFIIA、B、D、E、F和H的多蛋白复合物协同作用,以配体结合依赖的方式控制转录。在核受体介导的配体诱导的反式激活过程中,似乎涉及与AF-1和AF-2相互作用的核辅因子。最近已经鉴定出几种转录共激活因子和共抑制因子,它们的功能目前正在研究中。