Ainbinder Elena, Revach Merav, Wolstein Orit, Moshonov Sandra, Diamant Noam, Dikstein Rivka
Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel.
Mol Cell Biol. 2002 Sep;22(18):6354-62. doi: 10.1128/MCB.22.18.6354-6362.2002.
NF-kappaB induces the expression of genes involved in immune response, apoptosis, inflammation, and the cell cycle. Certain NF-kappaB-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-kappaB interacts directly with TAF(II)s, induction of NF-kappaB by tumor necrosis factor alpha (TNF-alpha) does not enhance TFIID recruitment and preinitiation complex formation on some NF-kappaB-responsive promoters. These promoters are bound by the transcription apparatus prior to TNF-alpha stimulus. Using the immediate-early TNF-alpha-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-kappaB. In vitro transcription assays confirmed that NF-kappaB 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-kappaB on the transcription process underlie the mechanism of their synergy and allow rapid transcriptional induction in response to cytokines.
核因子κB（NF-κB）可诱导参与免疫反应、细胞凋亡、炎症及细胞周期相关基因的表达。某些NF-κB反应性基因在细胞受到细胞因子和其他细胞外信号刺激后会迅速被激活。然而，这些基因被激活的机制尚未完全明确。在此我们报告，尽管NF-κB可直接与Ⅱ型TATA盒结合蛋白（TAF(II)s）相互作用，但肿瘤坏死因子α（TNF-α）诱导的NF-κB并不能增强某些NF-κB反应性启动子上TATA结合蛋白相关因子（TFIID）的募集及起始前复合物的形成。在TNF-α刺激之前，这些启动子就已被转录装置所结合。以早期即刻TNF-α反应性基因A20作为典型启动子，我们发现一般转录装置的组成性结合是由Sp1介导的，且这对于NF-κB的快速转录诱导至关重要。体外转录分析证实NF-κB发挥起始后作用，因为它可提高转录重新起始率，而起始步骤则需要Sp1。因此，Sp1和NF-κB在转录过程中的连续作用构成了它们协同作用的机制，并使得细胞能够对细胞因子做出快速转录诱导反应。
