v-Fps-responsiveness in the Egr-1 promoter is mediated by serum response elements.

v-Fps-responsiveness in the Egr-1 promoter is mediated by serum response elements.
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Egr-1 启动子中的 v-Fps 响应性由血清响应元件介导。

DOI:
10.1093/nar/20.9.2355
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发表时间:
1992
影响因子:
14.9
通讯作者:
Foster,DA
Foster,DA
中科院分区:
生物学2区
文献类型:
--
作者:
Alexandropoulos,K;Qureshi,SA;Rim,M;Sukhatme,VP;Foster,DA

文献摘要

被引文献

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Egr-1是一种有丝分裂原反应性转录因子,在蛋白质合成不存在的情况下被v-Fps快速诱导。因此,Egr-1是对v-Fps的蛋白酪氨酸激酶活性的主要应答。为了确定Egr-1启动子中的v-Fps响应元件,在瞬时表达测定中使用Egr-1启动子的缺失突变体。将v-Fps表达载体与氯霉素乙酰转移酶(CAT)基因表达载体共转染入NIH 3 T3细胞中,所述氯霉素乙酰转移酶(CAT)基因表达载体在Egr-1启动子或含有各种缺失的Egr-1启动子的控制下。对v-Fps的反应仅限于含有重复CC(A/T)6 GG序列的区域,称为CArG盒。CArG盒构成了血清反应元件(SRE)的核心。v-Fps诱导的Egr-1启动子激活通过顺序去除四个串联重复的SRE而丧失。该区域,含有四个SRE,被认为是足够的最大Egr-1诱导的v-Fps时,放置在上游的异源启动子。来自该区域的单个SRE能够响应v-Fps,然而,单个SRE的激活低于对成簇SRE观察到的激活。这些数据表明,在Egr-1启动子的v-Fps-响应性介导的SRE。
Egr-1, a mitogen-responsive transcription factor, is rapidly induced by v-Fps in the absence of protein synthesis. Thus, Egr-1 is a primary response to the protein-tyrosine kinase activity of v-Fps. To determine the v-Fps-responsive elements in the Egr-1 promoter, deletion mutants of the Egr-1 promoter were used in transient expression assays. A v-Fps expression vector was cotransfected into NIH 3T3 cells with chloramphenicol acetyl transferase (CAT) gene expression vectors under the control of the Egr-1 promoter or the Egr-1 promoter containing various deletions. Responsiveness to v-Fps was restricted to a region that contained repeated CC(A/T)6GG sequences, known as CArG boxes. CArG boxes form the core of serum response element (SREs). v-Fps induced Egr-1 promoter activation was lost by sequential removal of four tandemly repeated SREs. This region, containing four SREs, was found to be sufficient for maximal Egr-1 induction by v-Fps when placed upstream from a heterologous promoter. Individual SREs from this region were able to respond to v-Fps, however, the activation of the individual SREs was lower than that observed for the clustered SREs. These data suggest that v-Fps-responsiveness in the Egr-1 promoter is mediated by SREs.