CNBP acts as a key transcriptional regulator of sustained expression of interleukin-6

Eunhye Lee, Taeyun A. Lee, Ji Hyun Kim, Areum Park, Eun A. Ra, Sujin Kang, Hyun Jin Choi, Junhee L. Choi, Hyunbin D. Huh, Ji Eun Lee, Sungwook Lee, Boyoun Park

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Abstract

The transcription of inflammatory genes is an essential step in host defense activation. Here, we show that cellular nucleic acid-binding protein (CNBP) acts as a transcription regulator that is required for activating the innate immune response. We identified specific CNBP-binding motifs present in the promoter region of sustained inflammatory cytokines, thus, directly inducing the expression of target genes. In particular, lipopolysaccharide (LPS) induced cnbp expression through an NF-B-dependent manner and a positive autoregulatory mechanism, which enables prolonged il-6 gene expression. This event depends strictly on LPS-induced CNBP nuclear translocation through phosphorylation-mediated dimerization. Consequently, cnbp-depleted zebrafish are highly susceptible to Shigella flexneri infection in vivo. Collectively, these observations identify CNBP as a key transcriptional regulator required for activating and maintaining the immune response.

Original languageEnglish
Pages (from-to)3280-3296
Number of pages17
JournalNucleic acids research
Volume45
Issue number6
DOIs
Publication statusPublished - 2017 Jan 1

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All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Lee, E., Lee, T. A., Kim, J. H., Park, A., Ra, E. A., Kang, S., Choi, H. J., Choi, J. L., Huh, H. D., Lee, J. E., Lee, S., & Park, B. (2017). CNBP acts as a key transcriptional regulator of sustained expression of interleukin-6. Nucleic acids research, 45(6), 3280-3296. https://doi.org/10.1093/nar/gkx071