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

Nucleic Acids Res. 2017 Apr 7;45(6):3280-3296. doi: 10.1093/nar/gkx071.


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-κB-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • Consensus Sequence
  • Cytokines / genetics
  • Dysentery, Bacillary / immunology
  • Humans
  • Interleukin-12 Subunit p40 / genetics
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / genetics*
  • Mice
  • NF-kappa B / metabolism
  • Promoter Regions, Genetic
  • Protein Domains
  • Protein Multimerization
  • Protein Transport
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / metabolism*
  • Shigella flexneri
  • Transcription Factors / metabolism*
  • Transcriptional Activation*
  • Zebrafish


  • Cnbp1 protein, mouse
  • Cytokines
  • Interleukin-12 Subunit p40
  • Interleukin-6
  • NF-kappa B
  • RNA-Binding Proteins
  • Transcription Factors
  • interleukin-6, mouse