Cancer Center, La Jolla Cancer Research Foundation, La Jolla, CA 92037, USA.
Trends Endocrinol Metab. 1993 Jul;4(5):156-62. doi: 10.1016/1043-2760(93)90105-n.
Biologic responses to retinoids and thyroid hormones are mediated by their intracellular receptor proteins. Many exciting advances have been made recently in understanding the molecular mechanism by which these receptor proteins operate. In contrast to the steroid hormone receptors that function predominantly as homodimers, thyroid hormone receptors (TRs)and retinoic acid receptors (RARs) require interaction with the retinoid X receptors (RXRs) for efficient DNA binding and transactivation. In addition, RXRs, in the presence of their specific ligands such as 9-cis RA, can form homodimers that recognize a subset of retinoic acid responsive elements (RAREs). The retinoid responses mediated by RXR homodimers and RAR-RXR heterodimers can be restricted by the COUP-TF orphan receptors that bind strongly to certain RAREs as homodimers. Thus, a complex network of receptor interaction has been unraveled that promises a better understanding of thyroid and retinoid hormone regulation of fundamental biologic processes and diseases.
视黄酸和甲状腺激素的生物反应是由其细胞内受体蛋白介导的。最近在理解这些受体蛋白的作用的分子机制方面取得了许多令人兴奋的进展。与主要作为同源二聚体发挥作用的甾体激素受体不同，甲状腺激素受体 (TRs) 和视黄酸受体 (RARs) 需要与视黄酸 X 受体 (RXRs) 相互作用才能有效地进行 DNA 结合和转录激活。此外，在其特定配体（如 9-顺式 RA）的存在下，RXRs 可以形成同源二聚体，识别一组特定的视黄酸反应元件 (RAREs)。由 RXR 同源二聚体和 RAR-RXR 异源二聚体介导的视黄酸反应可以受到 COUP-TF 孤儿受体的限制，这些受体作为同源二聚体与某些 RAREs 结合紧密。因此，已经揭示了一个复杂的受体相互作用网络，有望更好地理解甲状腺和视黄酸激素对基本生物过程和疾病的调节。
