A regulatory element that mediates co‐operation between a PEA3‐AP‐1 element and an AP‐1 site is required for phorbol ester induction of urokinase enhancer activity in HepG2 hepatoma cells.
A regulatory element that mediates co‐operation between a PEA3‐AP‐1 element and an AP‐1 site is required for phorbol ester induction of urokinase enhancer activity in HepG2 hepatoma cells.
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佛波酯诱导 HepG2 肝癌细胞中的尿激酶增强剂活性需要介导 PEA3-AP-1 元件和 AP-1 位点之间合作的调节元件。
DOI：
10.1002/j.1460-2075.1992.tb05559.x
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
P. Verde
中科院分区：
文献类型：
--
作者：
C. Nerlov;D. De Cesare;F. Pergola;A. Caracciolo;F. Blasi;M. Johnsen;P. Verde
我们已经表征了人尿激酶型纤溶酶原激活物（uPA）基因的转录增强子，并发现了PEA 3-AP-1元件和增强子中AP-1位点之间合作所需的调控元件。我们将这种调节元件命名为合作中介体（COM）。PEA 3-AP-1元件、AP-1位点和COM都是HepG 2肝癌细胞系中从uPA启动子有效诱导佛波酯转录所必需的。我们发现，COM也需要PEA 3-AP-1元件和糖皮质激素反应元件之间的合作，无论是在TPA的存在或不存在，表明COM通常能够介导诱导增强子元件之间的协同作用。COM含有多个重叠的核蛋白结合位点，称为uPA增强因子1-4（UEF-1 - 4）。我们已经确定了UEF-1、UEF-2和UEF-3的假定结合位点。uPA增强子中的UEF-1和-3位点在物种之间高度保守。我们证明了UEF-3与NIP元件的结合，NIP元件是人白细胞介素-3和基质溶解素启动子中先前表征的调控元件，表明该因子在多种基因的调控中发挥作用。
We have characterized a transcriptional enhancer of the human urokinase‐type plasminogen activator (uPA) gene and found a regulatory element required for co‐operation between a PEA3‐‐AP‐1 element and an AP‐1 site in the enhancer. We designated this regulatory element co‐operation mediator (COM). Both the PEA3‐‐AP‐1 element, the AP‐1 site and the COM are required for efficient phorbol ester induction of transcription from the uPA promoter in the HepG2 hepatoma cell line. We show that the COM is also required for co‐operation between the PEA3‐‐AP‐1 element and a glucocorticoid response element, both in the presence or absence of TPA, indicating that the COM is generally capable of mediating synergism between inducible enhancer elements. The COM contains multiple overlapping binding sites for nuclear proteins, designated uPA enhancer factors 1–4 (UEF‐1‐4). We have identified putative binding sites for UEF‐1, −2 and −3. The UEF‐1 and −3 sites in the uPA enhancer are highly conserved between species. We demonstrate the binding of UEF‐3 to the NIP element, a previously characterized regulatory element in the human interleukin‐3 and stromelysin promoters, suggesting that this factor plays a role in regulation of a variety of genes.