First Author | Lee E | Year | 2017 |
Journal | Nucleic Acids Res | Volume | 45 |
Issue | 6 | Pages | 3280-3296 |
PubMed ID | 28168305 | Mgi Jnum | J:246205 |
Mgi Id | MGI:5924232 | Doi | 10.1093/nar/gkx071 |
Citation | Lee E, et al. (2017) CNBP acts as a key transcriptional regulator of sustained expression of interleukin-6. Nucleic Acids Res 45(6):3280-3296 |
abstractText | 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-kappaB-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. |