Cross-talk between transcription factors NF-κB and C/EBP in the transcriptional regulation of genes
Cross-talk between transcription factors NF-κB and C/EBP in the transcriptional regulation of genes
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DOI：
10.1016/s1357-2725(97)00083-6
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发表时间：
1997-12-01
影响因子：
4
通讯作者：
Woo, P
中科院分区：
文献类型：
--
作者：
Xia, CL;Cheshire, JK;Woo, P
对急性期反应的研究已经引起了极大的兴趣，不仅因为其医学意义，而且因为其作为一种极好的系统的提供，利用该系统来阐明涉及基因表达调节的分子机制，我们以前的数据表明，白细胞介素-1（IL-1）和白细胞介素-6（IL-6）协同诱导主要急性期反应物血清淀粉样蛋白A2（SAA 2）表达，是由两个家族的转录因子，即NF-κ B和C/EBP介导的，为了理解这种协同作用的分子机制，我们对参与调节复合物形成的因子进行了分子解剖，电泳迁移率变动分析表明NF-κ B p65（RelA）和p50，而不是p52或c-Rel，响应IL-1刺激特异性结合SAA 2启动子的NF-κ B位点。此外，C/EBP β和C/EBP δ，而不是C/EBP α，响应IL-6刺激特异性结合SAA 2的C/EBP位点，瞬时共转染分析表明NF-κ B p65与C/EBP β，特别是与C/EBP δ的协同结合导致SAA 2启动子的协同转录激活。当一起孵育时，NF-κ B p65和C/EBP β通过直接的蛋白质/蛋白质相互作用形成三元复合物。突变分析表明，Rel同源结构域（RHD）的C-末端区域和p65的活化结构域的C-末端对于其与C/EBP β的相互作用是重要的，这些结果表明NF-κ B和C/EBP可以形成新的转录因子复合物，其介导IL-1和IL-6对SAA 2的协同诱导，（C）1997 Elsevier Science Ltd，All rights reserved.
The study of the acute phase response has attracted substantial interest, not only for its medical implication, but also its provision as an excellent system with which to elucidate the molecular mechanisms involved in the modulation of gene expression, Our previous data suggest that the synergistic induction of the major acute phase reactant serum amyloid A2 (SAA2) expression by interleukin-1 (IL-1) and interleukin-6 (IL-6) is mediated by two families of transcription factors, namely NF-kappa B and C/EBP, To understand the molecular mechanisms of this synergy, we have undertaken a molecular dissection of the factors involved in the formation of the regulatory complex, Electrophoretic mobility shift analysis indicates that NF-kappa B p65 (RelA) and p50, but not p52 or c-Rel, bind specifically to the NF-kappa B site of the SAA2 promoter in response to IL-I stimulation, In addition, C/EBP beta and C/EBP delta, but not C/EBP alpha, bind specifically to the C/EBP site of SAA2 in response to IL-6 stimulation, Transient co-transfection analysis indicates that co-operative association of NF-kappa B p65 with C/EBP beta and, in particular, with C/EBP delta, results in synergistic transcriptional activation of the SAA2 promoter, When incubated together, NF-kappa B p65 and C/EBP beta form a ternary complex by direct protein/protein interaction, Mutational analysis demonstrates that the C-terminus region of the Rel homology domain (RHD) and the C-terminus of the activation domain of p65 are important for its interaction with C/EBP beta, These results suggest the NF-kappa B and C/EBP may form a new complex of transcription factors that mediates the synergistic induction of SAA2 by IL-1 and IL-6, (C) 1997 Elsevier Science Ltd, All rights reserved.