期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 289, 期 18, 页码 12876-12885出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M113.535831
关键词
DNA-binding Protein; Interleukin; Kruppel-like factor (KLF); NF-B (NF-B); Signal Transduction; Transcription; Tumor Necrosis Factor (TNF)
资金
- Ministry of Science and Technology of China [2012CB910201, 2010CB911800, 2014CB542600]
- National Natural Science Foundation of China [31221061, 31130020, 31371427, 91029302]
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.
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