Kruppel-like Factor 6 Is a Co-activator of NF- κB That Mediates p65-dependent Transcription of Selected Downstream Genes
Kruppel-like Factor 6 Is a Co-activator of NF- κB That Mediates p65-dependent Transcription of Selected Downstream Genes
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DOI：
10.1074/jbc.m113.535831
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发表时间：
2014-05-02
影响因子：
4.8
通讯作者：
Shu, Hong-Bing
中科院分区：
文献类型：
--
作者：
Zhang, Yu;Lei, Cao-Qi;Shu, Hong-Bing
背景：转录因子NF-B参与多种生物过程，并在多个水平上受到调控。结果：KLF6通过促进p65与下游基因启动子的结合来调节nf - b介导的转录。结论：KLF6是nf - b介导的特定下游基因转录的共激活因子。意义：我们的研究揭示了nf - b介导的细胞核转录激活的一种新的调控机制。转录因子NF-B在包括发育、炎症和免疫在内的广泛的生理和病理过程中起着关键作用。NF-B如何将激活信号整合到特定靶基因的表达中是非常有趣的。在这里，我们发现kruppel样因子6 （KLF6）是TNF和IL-1刺激后NF-B的共同激活因子。过表达KLF6会增强TNF-和il -1诱导NF-B的激活和下游基因亚群的转录，而敲低KLF6则会产生相反的效果。KLF6在细胞核中与p65相互作用，并结合到靶基因的启动子上。在IL-1刺激下，KLF6以p65依赖的方式被募集到NF-B靶基因子集的启动子上，这反过来又需要p65与靶基因启动子的最佳结合。因此，我们的研究结果确定了KLF6是一种以前未知但必不可少的NF-B共激活因子，并为p65依赖性基因表达的分子调控提供了新的见解。
Background: Transcription factor NF-B is involved in various biological processes and regulated at multiple levels. Results: KLF6 modulates NF-B-mediated transcription by promoting binding of p65 to promoters of downstream genes. Conclusion: KLF6 is a co-activator of NF-B-mediated transcription of selected downstream genes. Significance: Our study reveals a new regulatory mechanism for NF-B-mediated transcriptional activation in the nucleus.The transcription factor NF-B plays a pivotal role in a broad range of physiological and pathological processes, including development, inflammation, and immunity. How NF-B integrates activating signals to expression of specific sets of target genes is of great interest. Here, we identified Kruppel-like factor 6 (KLF6) as a co-activator of NF-B after TNF and IL-1 stimulation. Overexpression of KLF6 enhanced TNF- and IL-1-induced activation of NF-B and transcription of a subset of downstream genes, whereas knockdown of KLF6 had opposite effects. KLF6 interacted with p65 in the nucleus and bound to the promoters of target genes. Upon IL-1 stimulation, KLF6 was recruited to promoters of a subset of NF-B target genes in a p65-dependent manner, which was in turn required for the optimal binding of p65 to the target gene promoters. Our findings thus identified KLF6 as a previously unknown but essential co-activator of NF-B and provided new insight into the molecular regulation of p65-dependent gene expression.