Danielsen M, Hinck L, Ringold G M
Department of Pharmacology, Stanford University School of Medicine, California 94305.
Cell. 1989 Jun 30;57(7):1131-8. doi: 10.1016/0092-8674(89)90050-0.
The specificity of target gene activation by steroid receptors is encoded within a small, cysteine-rich domain that is believed to form two zinc-coordinated fingers. Here we show that the ability of glucocorticoid and estrogen receptors to discriminate between their closely related response elements resides in the two amino acids located between the two cysteines in the C-terminal half of the first finger. Unexpectedly, chimeric glucocorticoid receptors harboring portions of the interfinger and/or second finger of the estrogen receptor have the ability to activate transcription from either a GRE- or ERE-containing promoter. We surmise that whereas the "knuckle" region of the first finger may be the primary determinant of sequence recognition, the remainder of the DNA binding domain normally confers structural information required for preventing promiscuous HRE recognition.
类固醇受体对靶基因激活的特异性编码在一个小的富含半胱氨酸的结构域内，该结构域被认为形成两个锌配位指。我们在此表明，糖皮质激素和雌激素受体区分其密切相关反应元件的能力存在于第一个指的C端一半中两个半胱氨酸之间的两个氨基酸。出乎意料的是，含有雌激素受体指间部分和/或第二个指的嵌合糖皮质激素受体能够从含有GRE或ERE的启动子激活转录。我们推测，虽然第一个指的“关节”区域可能是序列识别的主要决定因素，但DNA结合结构域的其余部分通常赋予防止混杂的HRE识别所需的结构信息。
