CONSTITUTIVE AND IL-6-INDUCED NUCLEAR FACTORS THAT INTERACT WITH THE HUMAN C-REACTIVE PROTEIN PROMOTER
CONSTITUTIVE AND IL-6-INDUCED NUCLEAR FACTORS THAT INTERACT WITH THE HUMAN C-REACTIVE PROTEIN PROMOTER
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DOI：
10.1002/j.1460-2075.1990.tb08131.x
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发表时间：
1990-02-01
期刊：
影响因子：
11.4
通讯作者：
CILIBERTO, G
中科院分区：
文献类型：
--
作者：
MAJELLO, B;ARCONE, R;CILIBERTO, G
在急性炎症期间，白细胞介素-6（IL-6）诱导人C-反应蛋白（CRP）基因的转录。诱导型CRP表达的重要信息位于转录起始位点之前的90个碱基内。我们表明CRP启动子含有两个相邻的结合位点（β.和α）与至少两种肝细胞特异性核蛋白H-APF-1和H-APF-2相互作用。消除或减少结合的点突变显著影响CRP基因表达水平。绑定到β当使用来自未诱导的或IL-6诱导的Hep 3B细胞的提取物时是相同的。相反，α的量变和质变都是不可逆的。可以用来自未诱导的细胞或来自用IL-6或IL-6+放线菌酮处理的细胞的提取物检测结合。一种基于多聚化的β-结合结构域，但不是α-结构域，是高度可诱导的，当转染在肝癌细胞。这些结果进行了讨论，其他急性期诱导基因的启动子区域的结构。
Transcription of the human C-reactive protein (CRP) gene is induced by interleukin-6 (IL-6) during acute inflammation. Important information for inducible CRP expression is located within the 90 bases preceding the transcriptional start site. We show that the CRP promoter contains two adjacent binding sites (.beta. and .alpha.) that interact with at least two hepatocyte-specific nuclear proteins, H-APF-1 and H-APF-2. Point mutations that abolish or reduce binding drastically affect the level of CRP gene expression. Binding to .beta. is identical when extracts from uninduced or IL-6 induced Hep3B cells are used. On the contrary, both quantitative and qualitative changes in the .alpha. binding can be detected with extracts from uninduced cells or from cells treated with IL-6 or IL-6+ cycloheximide. A synthetic promoter based on the multimerization of the .beta.-binding domain, but not of the .alpha.-domain, is highly inducible when transfected in hepatoma cells. These results are discussed in relation to the structure of the promoter region of other acute phase inducible genes.