DNA Recognition by Normal and Oncogenic Thyroid Hormone Receptors

DNA Recognition by Normal and Oncogenic Thyroid Hormone Receptors
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正常和致癌甲状腺激素受体对 DNA 的识别

DOI:
--
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发表时间:
1996
影响因子:
4.8
通讯作者:
M. Privalsky
M. Privalsky
中科院分区:
生物学2区
文献类型:
--
作者:
Catherine Judelson;M. Privalsky

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核激素受体调节靶基因的表达,以响应细胞外来源的激素。因此,这些受体的DNA结合特异性在确定对特定激素作出反应的目标基因的精确谱系中起着关键作用。我们报告了甲状腺激素受体(c-erba蛋白)和致癌衍生物v-erba蛋白的DNA结合特异性的分析。这些在其他方面非常相似的蛋白质在DNA结合位点内的多个位置上表现出非常不同的DNA序列特异性。甲状腺激素受体(c-erba蛋白)表现出特别广泛的DNA特异性,而v-erba蛋白则相对具有相当的特异性。有趣的是,DNA识别的这些差异很大程度上映射到N端受体结构域,传统上并不涉及DNA结合,并进一步受到与维甲酸X受体形成的异源二聚体的影响。我们认为,核激素受体的N端通过改变进行碱基特异性接触的受体结构域的构象,在DNA识别中发挥关键作用。
The nuclear hormone receptors regulate target gene expression in response to hormones of extracellular origin. The DNA binding specificity of these receptors therefore plays the critical role of defining the precise repertoire of target genes that respond to a given hormone. We report here an analysis of the DNA binding specificity of the thyroid hormone receptor (c-ErbA protein) and that of an oncogenic derivative, the v-ErbA protein. These otherwise closely similar proteins exhibit quite divergent DNA sequence specificities at multiple positions within the DNA binding site. The thyroid hormone receptor (c-ErbA protein) exhibits a particularly broad DNA specificity, whereas the v-ErbA protein is comparatively quite specific. Intriguingly, these differences in DNA recognition largely map to an N-terminal receptor domain not traditionally implicated in DNA binding, and are further influenced by heterodimer formation with retinoid X receptors. We propose that the N terminus of nuclear hormone receptors plays an critical role in DNA recognition by altering the conformation of the receptor domains that make the actual base-specific contacts.
DOI: 10.1016/0003-2697(91)90534-z
发表时间: 1991-02-01
影响因子: 2.9
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通讯作者: DIXON, JE
DOI: 10.1126/science.1314418
发表时间: 1992-04
期刊: Science
影响因子: 56.9
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通讯作者: Thomas E. Wilson;R. E. Paulsen;Kerstien A. Padgett;Jeffrey Milbrandt
DOI: 10.1073/pnas.92.2.422
发表时间: 1995-01-17
影响因子: 11.1
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通讯作者: PRIVALSKY, ML
无偏见地鉴定以高亲和力结合甲状腺激素受体 α1 的 DNA 序列。
DOI: --
发表时间: 1993
期刊: The Journal of biological chemistry
影响因子: --
作者:
Katz,RW;Koenig,RJ
通讯作者: Koenig,RJ