CNBP acts as a key transcriptional regulator of sustained expression of interleukin-6
- 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.
- Nucleic acids research 45: 3280-3296 (Journal)
- Registered Authors
- Lee, Eun-Hye, Lee, Ji Eun
- cytokine, transcription, genetic, immune response, cell nucleus, dimerization, genes, phosphorylation, promoter regions (genetics), interleukin-6, candidate disease gene
- MeSH Terms
- Base Sequence
- Cell Nucleus/metabolism
- Cells, Cultured
- Consensus Sequence
- Dysentery, Bacillary/immunology
- Interleukin-12 Subunit p40/genetics
- 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*
- 28168305 Full text @ Nucleic Acids Res.
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. 45:3280-3296.
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.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes