title: Krüppel-like factor 6 is a co-activator of NF-κB that mediates p65-dependent transcription of selected downstream genes.
abstract: The transcription factor NF-κB plays a pivotal role in a broad range of physiological and pathological processes, including development, inflammation, and immunity. How NF-κB integrates activating signals to expression of specific sets of target genes is of great interest. Here, we identified Krüppel-like factor 6 (KLF6) as a co-activator of NF-κB after TNFα and IL-1β stimulation. Overexpression of KLF6 enhanced TNFα- and IL-1β-induced activation of NF-κB 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-1β stimulation, KLF6 was recruited to promoters of a subset of NF-κB 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-κB and provided new insight into the molecular regulation of p65-dependent gene expression.
authors.affiliation: From the College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Cao-Qi
authors.initials: CQ
authors.lastname: Lei
authors.forename: Yun-Hong
authors.initials: YH
authors.lastname: Hu
authors.forename: Tian
authors.initials: T
authors.lastname: Xia
authors.forename: Mi
authors.initials: M
authors.lastname: Li
authors.forename: Bo
authors.initials: B
authors.lastname: Zhong
authors.forename: Hong-Bing
authors.initials: HB
authors.lastname: Shu
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D045325:HCT116 Cells; D057809:HEK293 Cells; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D053583:Interleukin-1beta; C105465:KLF6 protein, human; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha
keywords: DNA-binding Protein; Interleukin; Kruppel-like factor (KLF); NF-κB (NF-κB); Signal Transduction; Transcription; Tumor Necrosis Factor (TNF)