PMA induces expression from the herpes simplex virus thymidine kinase promoter via the activation of JNK and ERK in the presence of adenoviral E1A proteins.
PMA induces expression from the herpes simplex virus thymidine kinase promoter via the activation of JNK and ERK in the presence of adenoviral E1A proteins.
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在腺病毒 E1A 蛋白存在的情况下，PMA 通过激活 JNK 和 ERK 来诱导单纯疱疹病毒胸苷激酶启动子的表达。
DOI：
10.1016/j.abb.2009.08.013
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发表时间：
2009
影响因子：
3.9
通讯作者：
Hardin,JohnA
中科院分区：
文献类型：
--
作者：
Shifera,AmdeSelassie;Hardin,JohnA
单纯疱疹病毒1型（HSV-1）胸苷激酶（TK）启动子包含参与组成型和诱导型表达的元件。我们确定佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）在HEK 293细胞中诱导HSV-1 TK启动子。然而，PMA并不诱导HeLa细胞中启动子的表达，也不导致HEK 293细胞中基因表达的整体增加。HSV-1 TK启动子的诱导需要JNK和ERK途径的激活。然而，单独激活两条途径不足以诱导HSV-1 TK启动子。通过将HEK 293基因组中的E1 A基因瞬时转染到HeLa细胞中，我们证明了E1 A蛋白是PMA诱导HSV-1 TK启动子所必需的。我们提出了肿瘤启动子PMA激活的信号通路与癌基因E1 A合作刺激真核启动子，即HSV-1 TK启动子的机制。
The herpes simplex virus type 1 (HSV-1) thymidine kinase (TK) promoter contains elements involved in both constitutive and induced expression. We determined that phorbol 12-myristate 13-acetate (PMA) induces the HSV-1 TK promoter in HEK293 cells. However, PMA did not induce expression from the promoter in HeLa cells and did not result in a globally increased gene expression in HEK293 cells. Induction of HSV-1 TK promoter required activation of both of JNK and ERK pathways. However, activation of the two pathways alone was not sufficient for induction of HSV-1 TK promoter. By transiently transfecting into HeLa cells the adenoviral E1A gene, which exists as an integrant in HEK293 genome, we demonstrated that E1A proteins are necessary for induction of HSV-1 TK promoter by PMA. We propose mechanisms by which signaling pathways activated by the tumor-promoter PMA cooperate with the oncogene E1A to stimulate a eukaryotic promoter, namely the HSV-1 TK promoter.