Regulation of parathyroid hormone-related protein gene expression in murine keratinocytes by E1A isoforms: a role for basal promoter and Ets-1 site.
Regulation of parathyroid hormone-related protein gene expression in murine keratinocytes by E1A isoforms: a role for basal promoter and Ets-1 site.
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E1A 同种型对小鼠角质形成细胞中甲状旁腺激素相关蛋白基因表达的调节：基础启动子和 Ets-1 位点的作用。
DOI：
10.1016/s0303-7207(99)00151-3
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发表时间：
1999
影响因子：
4.1
通讯作者：
Philbrick,WM
中科院分区：
文献类型：
--
作者：
Foley,J;Wysolmerski,JJ;Missero,C;King,CS;Philbrick,WM
PTHrP基因的表达进行了评估，在鼠角质形成细胞系，Pam 212 K，转化E1 A和ras。我们发现，12 S-E1 A癌基因，有或没有ras转化，显着降低PTHrP mRNA的表达。使用瞬时转染实验，我们发现12 S异构体抑制5′ PTHrP驱动的报告基因的活性。E1 A诱导的PTHrP报告构建体的抑制似乎是由最小启动子区域内的序列介导的。13 S-E1 A亚型不抑制PTHrP报告基因活性，并且缺乏阻遏物结构域的13 S缺失突变体激活了报告构建体的子集。基础启动子上游的Ets-1结合位点的突变显著降低了该13 S-缺失突变体对报告构建体的激活。这些发现表明，E1 A癌蛋白可能作为一个模型，激活和抑制PTHrP基因的表达。
PTHrP gene expression was evaluated in a murine keratinocyte line, Pam 212K, transformed with E1A and ras. We found that the 12S-E1A oncogene, with or without ras transformation, markedly reduced PTHrP mRNA expression. Using transient transfection assays, we found that the 12S isoform repressed activity from a 5′PTHrP-driven reporter gene. E1A-induced repression of PTHrP reporter constructs appears to be mediated by sequences within minimal promoter region. The 13S-E1A isoform did not repress PTHrP reporter gene activity, and a 13S-deletion mutant that lacked the repressor domains activated a subset of reporter constructs. Mutation of an Ets-1 binding site upstream of the basal promoter substantially decreased activation of reporter constructs by this 13S-deletion mutant. These findings suggest that the E1A oncoprotein may serve as a model for both activation and repression of PTHrP gene expression.