PUBLICATION

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

Authors
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.
ID
ZDB-PUB-170421-12
Date
2017
Source
Nucleic acids research   45: 3280-3296 (Journal)
Registered Authors
Lee, Eun-Hye, Lee, Ji Eun
Keywords
cytokine, transcription, genetic, immune response, cell nucleus, dimerization, genes, phosphorylation, promoter regions (genetics), interleukin-6, candidate disease gene
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
(all 23)
PubMed
28168305 Full text @ Nucleic Acids Res.
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-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
Marker Marker Type Name
cnbpaGENECCHC-type zinc finger, nucleic acid binding protein a
cnbpbGENECCHC-type zinc finger, nucleic acid binding protein b
gapdhsGENEglyceraldehyde-3-phosphate dehydrogenase, spermatogenic
il6GENEinterleukin 6 (interferon, beta 2)
tnfaGENEtumor necrosis factor a (TNF superfamily, member 2)
1 - 5 of 5
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Figures
Figure Gallery (2 images)
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Expression
Gene Antibody Fish Conditions Stage Qualifier Anatomy Assay Figure
il6WTchemical treatment by injection: lipopolysaccharidePrim-5RTPCR
il6WT + MO2-cnbpachemical treatment by injection: lipopolysaccharidePrim-5RTPCR
il6WT + MO3-cnbpachemical treatment by injection: lipopolysaccharidePrim-5RTPCR
1 - 3 of 3
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Phenotype
Fish Conditions Stage Phenotype Figure
WTchemical treatment by injection: lipopolysaccharidePrim-5
WT + MO2-cnbpachemical treatment by injection: lipopolysaccharidePrim-5
WT + MO2-cnbpachemical treatment by injection: lipopolysaccharideProtruding-mouth
WT + MO2-cnbpabacterial treatment by injection: Shigella flexneriProtruding-mouth
WT + MO2-cnbpabacterial treatment by injection: Shigella flexneriProtruding-mouth to Day 4
WT + MO3-cnbpachemical treatment by injection: lipopolysaccharidePrim-5
WT + MO3-cnbpachemical treatment by injection: lipopolysaccharideProtruding-mouth
WT + MO3-cnbpabacterial treatment by injection: Shigella flexneriProtruding-mouth
WT + MO3-cnbpabacterial treatment by injection: Shigella flexneriProtruding-mouth to Day 4
1 - 9 of 9
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Mutations / Transgenics
No data available
Human Disease / Model
No data available
Sequence Targeting Reagents
Target Reagent Reagent Type
cnbpaMO2-cnbpaMRPHLNO
cnbpaMO3-cnbpaMRPHLNO
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Fish
Fish
WT
WT + MO2-cnbpa
WT + MO3-cnbpa
1 - 3 of 3
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Antibodies
Orthology
Engineered Foreign Genes
No data available
Mapping
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Citation
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.