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首页> 外文期刊>Molecular and Cellular Biology >Role of Tissue-Specific Transcription Factor LFB3 in a Cyclic AMP-Responsive Enhancer of the Urokinase-Type Plasminogen Activator Gene in LLC-PK1 Cells
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Role of Tissue-Specific Transcription Factor LFB3 in a Cyclic AMP-Responsive Enhancer of the Urokinase-Type Plasminogen Activator Gene in LLC-PK1 Cells

机译：组织特异性转录因子LFB3在LLC-PK1细胞中尿激酶型纤溶酶原激活基因的环AMP响应增强子中的作用。

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摘要

A cyclic AMP (cAMP)-inducible enhancer in the pig urokinase-type plasminogen activator gene located 3.4 kb upstream of the transcription initiation site is composed of three protein-binding domains, A, B, and C. Domains A and B each contain a CRE (cAMP response element)-like sequence but require the adjoining C domain for full cAMP responsiveness. A tissue-specific transcription factor, LFB3/HNF1β/vHNF1, binds to the C domain. Mutation analyses suggest that the imperfect CRE and LFB3-binding sequences are required for tight coupling of hormonal and tissue-specific regulation. CREB and ATF1 bind to domains A and B, and this binding is enhanced upon phosphorylation by cAMP-dependent protein kinase (protein kinase A [PKA]). Analysis in a mammalian two-hybrid system revealed that CREB/ATF1 and LFB3 interact and that transactivation potential is enhanced by PKA activation. Interestingly, however, phosphorylation of CREB at Ser-133 does not contribute to its interaction with LFB3. The region of LFB3 involved in its interaction with CREB/ATF1 lies, at least partly, between amino acids 400 and 450. Deletion of this region removed the ability of LFB3 to mediate cAMP induction of the ABC enhancer but did not impair its basal transactivation activity on the albumin promoter. Thus, the two activities are distinct functions of LFB3.
机译：位于转录起始位点上游3.4 kb的猪尿激酶型纤溶酶原激活物基因中的环AMP（cAMP）诱导型增强子由三个蛋白质结合结构域A，B和C组成。结构域A和B各自包含一个CRE（cAMP响应元件）类似的序列，但需要相邻的C结构域才能完全cAMP响应。组织特异性转录因子LFB3 /HNF1β/ vHNF1与C结构域结合。突变分析表明，不完美的CRE和LFB3结合序列是激素和组织特异性调节紧密结合所必需的。 CREB和ATF1与域A和B结合，而这种结合在依赖cAMP的蛋白激酶（蛋白激酶A [PKA]）磷酸化后得以增强。在哺乳动物双杂交系统中的分析表明，CREB ​​/ ATF1和LFB3相互作用，并且通过PKA激活增强了反式激活的潜力。然而，有趣的是，CREB在Ser-133的磷酸化并没有促进其与LFB3的相互作用。 LFB3与CREB ​​/ ATF1相互作用所涉及的区域至少部分位于氨基酸400和450之间。该区域的缺失去除了LFB3介导cAMP诱导ABC增强子的能力，但不损害其基础反式激活活性在白蛋白启动子上。因此，这两个活动是LFB3的不同功能。

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