MAPK and JNK transduction pathways can phosphorylate Sp1 to activate the uPA minimal promoter element and endogenous gene transcription
MAPK and JNK transduction pathways can phosphorylate Sp1 to activate the uPA minimal promoter element and endogenous gene transcription
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DOI：
10.1182/blood-2003-08-2661
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发表时间：
2004-07-01
期刊：
影响因子：
20.3
通讯作者：
Crippa, MP
中科院分区：
文献类型：
--
作者：
Benasciutti, E;Pagès, G;Crippa, MP
人尿激酶（uPA）基因的两个上游区域调节其转录：最小启动子（MP）和增强子元件。最小启动子的活性对前列腺癌PC 3细胞中uPA的基础转录是必需的。磷酸化Sp1转录因子的结合反过来又是MP活性所必需的。在这里，我们报告说，Jun激酶（JNK）途径所需的IMP的基础活性和内源性uPA基因在PC 3细胞中的表达和LNCaP细胞中的激活转录。另一方面，p42/p44丝裂原活化蛋白激酶（MAPK）途径通过HeLa、LNCaP和CCL 39衍生细胞中的Sp1磷酸化激活uPA基因表达，这些细胞在基础条件下通常不表达uPA。在HeLa细胞中，JNK的显性负性形式干扰uPA-MP的p42/p44 MAPK活化。结果表明，应激活化蛋白激酶（SAPK）/JNK途径在Sp1的磷酸化中起着重要作用，这反过来又导致uPA-MP元件的基础或激活转录。
Two upstream regions of the human urokinase (uPA) gene regulate its transcription: the minimal promoter (MP) and the enhancer element. The activity of the minimal promoter is essential for basal uPA transcription in prostate adenocarcinoma PC3 cells. Binding of a phosphorylated Sp1 transcription factor is, in turn, essential for the activity of the MP. Here we report that the Jun kinase (JNK) pathway is required for the basal activity of the IMP and for the expression of the endogenous uPA gene in PC3 cells and for activated transcription in LNCaP cells. On the other hand, the p42/p44 mitogen-activated protein kinase (MAPK) pathway activates uPA gene expression through Sp1 phosphorylation in HeLa, LNCaP, and CCL39-derivative cells that do not typically express uPA in basal conditions. In HeLa cells the dominant-negative form of JNK interferes with the p42/p44 MAPK activation of the uPA-MP. The results suggest that the stress-activated protein kinase (SAPK)/JNK pathway plays an important role in the phosphorylation of Sp1, which, in turn, leads to basal or activated transcription from the uPA-MP element.