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首页> 外文期刊>Molecular and Cellular Biology >Mechanism of Rapid Transcriptional Induction of Tumor Necrosis Factor Alpha-Responsive Genes by NF-κB
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Mechanism of Rapid Transcriptional Induction of Tumor Necrosis Factor Alpha-Responsive Genes by NF-κB

机译：NF-κB快速转录诱导肿瘤坏死因子α反应性基因的机制

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NF-κB induces the expression of genes involved in immune response, apoptosis, inflammation, and the cell cycle. Certain NF-κB-responsive genes are activated rapidly after the cell is stimulated by cytokines and other extracellular signals. However, the mechanism by which these genes are activated is not entirely understood. Here we report that even though NF-κB interacts directly with TAFIIs, induction of NF-κB by tumor necrosis factor alpha (TNF-α) does not enhance TFIID recruitment and preinitiation complex formation on some NF-κB-responsive promoters. These promoters are bound by the transcription apparatus prior to TNF-α stimulus. Using the immediate-early TNF-α-responsive gene A20 as a prototype promoter, we found that the constitutive association of the general transcription apparatus is mediated by Sp1 and that this is crucial for rapid transcriptional induction by NF-κB. In vitro transcription assays confirmed that NF-κB plays a postinitiation role since it enhances the transcription reinitiation rate whereas Sp1 is required for the initiation step. Thus, the consecutive effects of Sp1 and NF-κB on the transcription process underlie the mechanism of their synergy and allow rapid transcriptional induction in response to cytokines.
机译：NF-κB诱导涉及免疫反应，细胞凋亡，炎症和细胞周期的基因表达。在细胞因子和其他细胞外信号刺激细胞后，某些NF-κB反应性基因被迅速激活。但是，尚未完全了解激活这些基因的机制。在这里，我们报道即使NF-κB与TAF II s直接相互作用，但肿瘤坏死因子α（TNF-α）对NF-κB的诱导并不能增强TFIID的募集和某些NF的预起始复合物的形成。 -κB反应性启动子。在TNF-α刺激之前，这些启动子被转录装置结合。使用立即早期的TNF-α反应基因A20作为原型启动子，我们发现一般转录装置的组成性缔合是由Sp1介导的，这对于NF-κB的快速转录诱导至关重要。体外转录测定证实了NF-κB起着后启动作用，因为它提高了转录的重新启动速率，而Sp1是启动步骤所必需的。因此，Sp1和NF-κB对转录过程的连续作用是它们协同作用的基础，并允许响应细胞因子而快速转录诱导。

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