CALCIUM AND GROWTH-FACTOR PATHWAYS OF C-FOS TRANSCRIPTIONAL ACTIVATION REQUIRE DISTINCT UPSTREAM REGULATORY SEQUENCES
CALCIUM AND GROWTH-FACTOR PATHWAYS OF C-FOS TRANSCRIPTIONAL ACTIVATION REQUIRE DISTINCT UPSTREAM REGULATORY SEQUENCES
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DOI：
10.1128/mcb.8.7.2787
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发表时间：
1988-07-01
影响因子：
5.3
通讯作者：
GREENBERG, ME
中科院分区：
文献类型：
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作者：
SHENG, M;DOUGAN, ST;GREENBERG, ME
c-fos原癌基因的转录在大鼠嗜铬细胞瘤PC 12细胞系中被多种刺激物快速诱导，包括多肽生长因子、佛波醇酯和钙离子流。我们已经绘制了上游序列的要求，这种激活在PC 12细胞通过分析启动子缺失突变体在瞬时表达试验。两种不同的c-fos诱导途径的定义，不同的要求顺式作用的DNA序列。钙激活c-fos转录依赖于位于转录起始位点上游约60个碱基对的DNA元件。该区域在人类、小鼠和鸡c-fos基因之间高度保守，并且包含类似于环AMP反应元件的共有序列。在位置-300处的二分体对称元件对于c-fos的血清反应性是必需的，对于该基因的钙激活似乎是不重要的。然而，二分体对称元件是c-fos由神经生长因子、表皮生长因子、成纤维细胞生长因子和佛波酯12-O-十四烷酰基佛波醇-13-乙酸酯诱导的必要顺式作用序列。在体内和体外的研究与二分体对称元素的各种突变体表明，c-fos激活多肽生长因子和12-O-十四烷酰基佛波醇-13-乙酸酯介导的一个共同的转录因子，这个因素是相同的，以前描述的血清反应因子。体外DNA结合试验表明，血清反应因子结合活性的数量在c-fos转录激活过程中保持不变。
Transcription of the c-fos proto-oncogene is rapidly induced in the rat pheochromocytoma PC12 cell line by a wide variety of stimuli, including polypeptide growth factors, phorbol esters, and calcium ion fluxes. We have mapped the upstream sequence requirements for this activation in PC12 cells by analysis of promoter deletion mutants in a transient expression assay. Two distinct pathways of c-fos induction are defined that differ in their requirement for cis-acting DNA sequences. Calcium activation of c-fos transcription is dependent on a DNA element located approximately 60 base pairs upstream of the transcription start site. This region is highly conserved between human, mouse, and chicken c-fos genes and contains a sequence that resembles the consensus for a cyclic AMP response element. The dyad symmetry element at position -300, which is necessary for serum responsiveness of c-fos, appears to be unimportant for calcium activation of the gene. The dyad symmetry element is, however, an essential cis-acting sequence for c-fos inducibility by nerve growth factor, epidermal growth factor, fibroblast growth factor, and the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate. Studies in vivo and in vitro with various mutants of the dyad symmetry element indicate that c-fos activation by polypeptide growth factors and 12-O-tetradecanoyl phorbol-13-acetate is mediated by a common transcription factor, and that this factor is identical to the previously described serum response factor. In vitro DNA-binding assays suggest that the quantity of serum response factor-binding activity remains unchanged during c-fos transcriptional activation.