Rhee M, Ikeda M, Chin W W
Department of Medicine, Brigham and Women's Hospital, Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA.
Endocrinology. 1995 Jun;136(6):2697-704. doi: 10.1210/endo.136.6.7750494.
The formation of heterodimers with thyroid hormone receptor (TR) and other nuclear hormone receptors on thyroid hormone response elements (TREs) is important for T3-regulated gene transcription. The potential roles of retinoid X receptor-alpha (RXR alpha) and apolipoprotein regulatory protein-1 (ARP-1) in T3-mediated transcription were studied on a well characterized TRE, a direct repeat of AGGTCA separated by four nucleotides (DR4), using electrophoretic mobility shift assays and transient transfection in CV-1 cells. It was shown that RXR alpha blocked liganded TR alpha-induced transcription. However, ARP-1 did not block T3/TR alpha-mediated transcription, although both TR alpha/RXR alpha and TR alpha/ARP-1 heterodimers had similar affinities for the TRE-DR4. In contrast, wild type ARP-1 reversed the blocking effect of RXR alpha on the liganded TR alpha-induced transcription, whereas a dimerization domain-deleted ARP-1 mutant (ARP-1 delta C) did not, suggesting that ARP-1 modulates T3-induced transcription through a dimerization process. Thus, the TRE-DR4 differentially responds to T3 at the transcriptional level by accommodating a battery of TR heterodimeric complexes.
甲状腺激素受体（TR）与其他核激素受体在甲状腺激素反应元件（TREs）上形成异源二聚体对于T3调节的基因转录很重要。利用电泳迁移率变动分析和CV-1细胞中的瞬时转染技术，在一个特征明确的TRE（由四个核苷酸隔开的AGGTCA直接重复序列，DR4）上研究了视黄酸X受体α（RXRα）和载脂蛋白调节蛋白-1（ARP-1）在T3介导的转录中的潜在作用。结果表明，RXRα阻断了配体结合的TRα诱导的转录。然而，尽管TRα/RXRα和TRα/ARP-1异源二聚体对TRE-DR4具有相似的亲和力，但ARP-1并未阻断T3/TRα介导的转录。相反，野生型ARP-1逆转了RXRα对配体结合的TRα诱导转录的阻断作用，而缺失二聚化结构域的ARP-1突变体（ARP-1ΔC）则没有，这表明ARP-1通过二聚化过程调节T3诱导的转录。因此，TRE-DR4通过容纳一系列TR异源二聚体复合物在转录水平上对T3产生不同的反应。
