Transcription factors modulating angiotensinogen gene expression in hepatocytes.
Transcription factors modulating angiotensinogen gene expression in hepatocytes.
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调节肝细胞中血管紧张素原基因表达的转录因子。
DOI：
10.1038/ki.1994.447
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发表时间：
1994
影响因子：
19.6
通讯作者：
A. Copland
中科院分区：
文献类型：
--
作者：
A. Brasier;J. Li;A. Copland
编码血管紧张素原的基因在肝细胞中的转录水平上受到糖皮质激素和炎症细胞因子（IL-1 和 TNF）的调节。这些激素通过改变与位于主要转录起始位点上游-615至-440核苷酸之间的多激素诱导增强子相互作用的DNA结合蛋白的丰度来激活血管紧张素原基因的转录。肝细胞中该增强子的激活受到糖皮质激素和细胞因子诱导的 DNA 结合蛋白的影响。细胞因子诱导是通过与急性期反应元件 (APRE) 结合的两类转录因子的相互作用介导的：核因子 kappa B (NF-kappa B) 和 CCAAT-Box/增强子结合蛋白 (C/EBP)。 NF-kappa B 是一种隔离在细胞质中的多蛋白 DNA 结合复合物，由细胞因子在细胞核中诱导，而 C/EBP 是与分化肝蛋白表达有关的核转录因子家族。在急性期反应期间，各个 C/EBP 家族成员受到不协调的调节：C/EBP α 水平下降，而另一个称为核因子 IL6 (NF-IL6) 的 C/EBP 家族成员被诱导。我们研究了两种急性期诱导的 APRE 结合蛋白：NF-κ B 和 NF-IL6 之间的相互作用。两种蛋白以相互排斥的方式与重叠的核苷酸结合，对 APRE 具有相似的亲和力。 NF-IL6 是一种效力较低的反式激活因子，可在急性期反应演化后期减弱 NF-κ B 介导的转录。这些观察结果支持了炎症过程演化过程中占据 APRE 的顺序表达转录因子的时间模型。
The gene encoding angiotensinogen is regulated at the transcriptional level in hepatocytes in response to glucocorticoids and inflammatory cytokines (IL-1 and TNF). These hormones activate transcription of the angiotensinogen gene by changing the abundance of DNA binding proteins that interact with a multihormone-inducible enhancer located between nucleotides -615 to -440 upstream of the major transcription start site. Activation of this enhancer in hepatocytes is effected by glucocorticoid- and cytokine-inducible DNA binding proteins. Cytokine induction is mediated through the interaction of two classes of transcription factors that bind to the acute-phase response element (APRE): nuclear factor-kappa B (NF-kappa B), and CCAAT-Box/Enhancer Binding Protein (C/EBP). NF-kappa B is a multiprotein DNA binding complex sequestered in the cytoplasm that is induced in the nucleus by cytokines, whereas C/EBP is a nuclear transcription factor family implicated in the expression of differentiated hepatic proteins. During the acute-phase response, individual C/EBP family members are discordinately regulated: C/EBP alpha levels fall, whereas another C/EBP family member termed nuclear factor IL6 (NF-IL6), is induced. We investigated the interaction between the two acute-phase induced APRE-binding proteins: NF-kappa B and NF-IL6. Both proteins bind to overlapping nucleotides in a mutually exclusive fashion with similar affinities for the APRE. NF-IL6, a less potent transactivator, attenuates NF-kappa B mediated transcription late in the evolution of the acute-phase response. These observations argue for a temporal model of sequentially-expressed transcription factors occupying the APRE during the evolution of the inflammatory process.
急性期诱导核因子-白细胞介素-6 转录因子中基本结构域-亮氨酸拉链 DNA 结合活性的新决定因素的鉴定。
DOI：
--
发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Brasier,AR;Kumar,A
通讯作者：
Kumar,A
血管紧张素原基因在大鼠胰岛细胞系中的新表达。
DOI：
--
发表时间：
1986
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Brasier,AR;Philippe,J;Campbell,DJ;Habener,JF
通讯作者：
Habener,JF