2 AMINO-ACIDS WITHIN THE KNUCKLE OF THE 1ST ZINC FINGER SPECIFY DNA RESPONSE ELEMENT ACTIVATION BY THE GLUCOCORTICOID RECEPTOR

2 AMINO-ACIDS WITHIN THE KNUCKLE OF THE 1ST ZINC FINGER SPECIFY DNA RESPONSE ELEMENT ACTIVATION BY THE GLUCOCORTICOID RECEPTOR
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DOI:
10.1016/0092-8674(89)90050-0
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发表时间:
1989-06-30
期刊:
影响因子:
64.5
通讯作者:
RINGOLD, GM
RINGOLD, GM
中科院分区:
生物学1区
文献类型:
--
作者:
DANIELSEN, M;HINCK, L;RINGOLD, GM

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靶基因被类固醇受体激活的特异性是在一个小的富含半胱氨酸的结构域内编码的,该结构域被认为形成两个锌协调的手指。在这里,我们发现糖皮质激素和雌激素受体区分密切相关的反应元件的能力存在于位于食指c端一半的两个半胱氨酸之间的两个氨基酸中。出乎意料的是,嵌合糖皮质激素受体含有雌激素受体中指和/或中指的部分,能够激活含有GRE或ere的启动子的转录。我们推测,尽管第一根手指的“指关节”区域可能是序列识别的主要决定因素,但DNA结合域的其余部分通常提供防止混杂HRE识别所需的结构信息。
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.