RARS AND RXRS - EVIDENCE FOR 2 AUTONOMOUS TRANSACTIVATION FUNCTIONS (AF-1 AND AF-2) AND HETERODIMERIZATION INVIVO
RARS AND RXRS - EVIDENCE FOR 2 AUTONOMOUS TRANSACTIVATION FUNCTIONS (AF-1 AND AF-2) AND HETERODIMERIZATION INVIVO
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DOI：
10.1002/j.1460-2075.1993.tb05889.x
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发表时间：
1993-06-01
期刊：
影响因子：
11.4
通讯作者：
CHAMBON, P
中科院分区：
文献类型：
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作者：
NAGPAL, S;FRIANT, S;CHAMBON, P
我们以前曾报道，维甲酸受体（RAR和RXR）的AB区含有转录激活功能，能够调节这些受体的C-末端DE区中存在的配体依赖性激活功能的活性。然而，我们不能证明这些AB区域具有类似于在类固醇激素受体的AB区域中发现的AF-1的自主激活功能。使用小鼠CRBPII启动子作为报告基因，我们现在报告，RAR α，β和γ的AB区，以及RXR α和γ的AB区，包含一个自主的，配体非依赖性激活功能，AF-1，它可以有效地协同AF-2。此外，AF-1解释了RXR α和γ对转录的配体非依赖性组成性激活。我们还表明，RAR和RXR优先异源二聚体在体内培养的细胞中的溶液中，通过存在于其E区的二聚化界面，无论全反式或9-顺式视黄酸的存在。此外，我们的研究结果表明，在体内培养的细胞中，在异二聚体相互作用容易发生的条件下，未观察到同二聚体相互作用，这与先前的观察结果一致，表明RAR-RXR异二聚体在体外与RA反应元件优先结合。
We have previously reported that the AB regions of retinoic acid receptors (RARs and RXRs) contain a transcriptional activation function capable of modulating the activity of the ligand-dependent activation function present in the C-terminal DE regions of these receptors. However, we could not demonstrate that these AB regions possess an autonomous activation function similar to the AF-1s found in the AB regions of steroid hormone receptors. Using the mouse CRBPII promoter as a reporter gene, we now report that the AB regions of RARalpha, beta and gamma, as well as those of RXRalpha and gamma, contain an autonomous, ligand-independent activation function, AF-1, which can efficiently synergize with AF-2s. Moreover, AF-1s account for the ligand-independent, constitutive activation of transcription by RXRalpha and gamma. We also show that RARs and RXRs preferentially heterodimerize in solution in cultured cells in vivo, through the dimerization interface present in their E region, irrespective of the presence of all-trans or 9-cis retinoic acid. Furthermore, our results indicate that homodimeric interactions are not observed in cultured cells in vivo under conditions where heterodimeric interactions readily occur, which is in agreement with previous observations showing the preferential binding of RAR-RXR heterodimers to RA response elements in vitro.