EGR1, EGR2, and EGR3 Activate the Expression of Their Coregulator NAB2 Establishing a Negative Feedback Loop in Cells of Neuroectodermal and Epithelial Origin
EGR1, EGR2, and EGR3 Activate the Expression of Their Coregulator NAB2 Establishing a Negative Feedback Loop in Cells of Neuroectodermal and Epithelial Origin
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DOI：
10.1002/jcb.22690
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发表时间：
2010-09-01
影响因子：
4
通讯作者：
Johnson, Judith P.
中科院分区：
文献类型：
--
作者：
Kumbrink, Joerg;Kirsch, Kathrin H.;Johnson, Judith P.
诱导型锌指转录因子EGR1。EGR2和EGR3调节许多参与分化、咆哮和应答细胞外信号的基因的表达。在黑色素瘤和癌细胞中，EGR 1激活NAB2的表达。在T淋巴细胞中，EGR2和EGR3抑制NAB2的表达，因此，我们研究了EGR2和EGR3对黑色素瘤和癌细胞中NAB2表达的影响。在这里，我们发现，与EGR i一样，EGR2和EGR3诱导了这些细胞中NAB2的表达。EGR1和EGR3协同作用于NA82启动子，是比EGR2 EGR EGR2-更有效的NAB2转录激活因子，EGR3诱导的NAB2启动子活性是通过类似的顺式调控元件介导的，每个EGR的激活都被NAB2抑制。动力学研究表明，EGR I的诱导导致NAB2的低表达，而EGR2和EGR3是最大和持续表达所必需的。我们的研究结果表明，在许多神经外胚层和上皮细胞中，EGR1、EGR2和EGR3激活了NAB2的转录，而NAB2的转录又被NAB2抑制，因此，通过sirna（或EGR1）降低EGR2或EGR3的表达会降低内源性NA82水平。这表明EGR因子和NAB2表达之间的复杂关系可能取决于细胞环境。J细胞。生物化学111。207 - 217年,2010年。(C) 2010 Wiley-Liss, Inc
The inducible zinc finger transcription factors EGR1. EGR2, and EGR3 regulate the expression of numerous genes involved in differentiation, growl h. and response to extracellular signals. Their activity is modulated in part through NAB2 which is induced by the same stimuli In melanoma and carcinoma cells EGR 1 activates NAB2 expression In T lymphocytes EGR2 and EGR3 have been shown to inhibit NAB2 expression Therefore, we investigated the influence of EGR2 and EGR3 on NAB2 expression in melanoma and carcinoma cells Here, we show that like EGR I. EGR2 and EGR3 induced NAB2 expression in these cells. EGR1 and EGR3 act in concert on the NA82 promoter and are mote potent activators of NAB2 transcription than EGR2 EGR EGR2-, and EGR3-induced NAB2 promoter activity is mediated through similar cis-regulatory elements and the activation by each EGR is repressed by NAB2 Kinetic studies suggest that induction of EGR I leads to low NAB2 expression, while EGR2 and EGR3 are necessary for maximal and sustained expression. As already shown (or EGR 1, reduction of EGR2 or EGR 3 expression by siRNAs reduced endogenous NA82 levels Depletion of EGR3 also resulted in a reduction of EGR2 levels confirming EGR2 as a target gene of EGR3 Our results suggest that in many cells of neuroeciodermal and epithelial origin EGR1, EGR2, and EGR3 activate NAB2 transcnption which is in turn repressed by NAB2, thus establishing a negative feedback loop This points to a complex relationship between the EGR factors and NAB2 expression likely depending on the cellular context. J Cell. Biochem 111. 207-217, 2010. (C) 2010 Wiley-Liss, Inc