Krüppel-like factor 6 is a co-activator of NF-κB that mediates p65-dependent transcription of selected downstream genes.
J Biol Chem
; 289(18): 12876-85, 2014 May 02.
Article
em En
| MEDLINE
| ID: mdl-24634218
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-1ß stimulation. Overexpression of KLF6 enhanced TNFα- and IL-1ß-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-1ß 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.
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MEDLINE
Assunto principal:
Transcrição Gênica
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NF-kappa B
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Proteínas Proto-Oncogênicas
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Fatores de Transcrição Kruppel-Like
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Fator de Transcrição RelA
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article