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

Research output: Contribution to journalArticle

6 Citations (Scopus)

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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Nucleic Acids
Interleukin-6
Carrier Proteins
Lipopolysaccharides
Shigella flexneri
Gene Expression
Amino Acid Motifs
Essential Genes
Dimerization
Zebrafish
Protein Transport
Innate Immunity
Genetic Promoter Regions
Protein Binding
Phosphorylation
Cytokines
Infection

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Lee, Eunhye ; Lee, Taeyun A. ; Kim, Ji Hyun ; Park, Areum ; Ra, Eun A. ; Kang, Sujin ; Choi, Hyun Jin ; Choi, Junhee L. ; Huh, Hyunbin D. ; Lee, Ji Eun ; Lee, Sungwook ; Park, Boyoun. / CNBP acts as a key transcriptional regulator of sustained expression of interleukin-6. In: Nucleic Acids Research. 2017 ; Vol. 45, No. 6. pp. 3280-3296.
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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.",
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Lee, E, Lee, TA, Kim, JH, Park, A, Ra, EA, Kang, S, Choi, HJ, Choi, JL, Huh, HD, Lee, JE, Lee, S & Park, B 2017, 'CNBP acts as a key transcriptional regulator of sustained expression of interleukin-6', Nucleic Acids Research, vol. 45, no. 6, pp. 3280-3296. https://doi.org/10.1093/nar/gkx071

CNBP acts as a key transcriptional regulator of sustained expression of interleukin-6. / Lee, Eunhye; Lee, Taeyun A.; Kim, Ji Hyun; Park, Areum; Ra, Eun A.; Kang, Sujin; Choi, Hyun Jin; Choi, Junhee L.; Huh, Hyunbin D.; Lee, Ji Eun; Lee, Sungwook; Park, Boyoun.

In: Nucleic Acids Research, Vol. 45, No. 6, 01.01.2017, p. 3280-3296.

Research output: Contribution to journalArticle

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AU - Lee, Eunhye

AU - Lee, Taeyun A.

AU - Kim, Ji Hyun

AU - Park, Areum

AU - Ra, Eun A.

AU - Kang, Sujin

AU - Choi, Hyun Jin

AU - Choi, Junhee L.

AU - Huh, Hyunbin D.

AU - Lee, Ji Eun

AU - Lee, Sungwook

AU - Park, Boyoun

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AB - 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.

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