Saatcioglu F, Deng T, Karin M
Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla 92093-0636.
Cell. 1993 Dec 17;75(6):1095-105. doi: 10.1016/0092-8674(93)90319-l.
A novel type of hormone-responsive element (HRE) is described. Unlike classical HREs, this element, RSV-T3RE (found in Rous sarcoma virus-long terminal repeat), mediates strong activation by the c-ErbA alpha thyroid hormone (T3) receptor in the absence of T3, and addition of T3 reverses this response. Whereas both c-ErbA alpha and v-ErbA are potent ligand-independent activators through the RSV-T3RE, c-ErbA beta is not. The RSV-T3RE is recognized and activated by either c-ErbA alpha homodimers or c-ErbA alpha/retinoid X receptor (RXR) heterodimers. Ligand-independent activation by c-ErbA alpha depends on a unique N-terminal activation domain, while the C-terminal activation domain is not absolutely required. Ligand-dependent activation, on the other hand, requires the C-terminal but not the N-terminal activation domain. Upon binding to the RSV-T3RE, c-ErbA alpha assumes a different conformation than when bound to a classical T3RE. c-ErbA alpha is therefore capable of selective deployment of activation domains, dictated both by the HRE with which it interacts and by T3 binding.
描述了一种新型的激素反应元件（HRE）。与经典的HRE不同，这种元件，即RSV-T3RE（存在于劳氏肉瘤病毒长末端重复序列中），在没有三碘甲状腺原氨酸（T3）的情况下介导c-ErbAα甲状腺激素（T3）受体的强烈激活，而添加T3会逆转这种反应。虽然c-ErbAα和v-ErbA通过RSV-T3RE都是有效的非配体依赖性激活剂，但c-ErbAβ不是。RSV-T3RE被c-ErbAα同二聚体或c-ErbAα/视黄酸X受体（RXR）异二聚体识别并激活。c-ErbAα的非配体依赖性激活取决于一个独特的N端激活结构域，而C端激活结构域不是绝对必需的。另一方面，配体依赖性激活需要C端但不需要N端激活结构域。与RSV-T3RE结合后，c-ErbAα呈现出与结合经典T3RE时不同的构象。因此，c-ErbAα能够根据与其相互作用的HRE和T3结合情况选择性地部署激活结构域。
