CNBP acts as a key transcriptional regulator of sustained expression of interleukin-6.
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.
Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, South Korea.
Eunhye
E
Lee
Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, South Korea.
Taeyun A
TA
Lee
Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul 06351, South Korea.
Ji Hyun
JH
Kim
Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, South Korea.
Areum
A
Park
Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, South Korea.
Eun A
EA
Ra
Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, South Korea.
Sujin
S
Kang
Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, South Korea.
Hyun Jin
HJ
Choi
Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, South Korea.
Junhee L
JL
Choi
Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, South Korea.
Hyunbin D
HD
Huh
Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul 06351, South Korea.|Samsung Genome Institute (SGI), Samsung Medical Center, Seoul 06351, South Korea.
Ji Eun
JE
Lee
Cancer Immunology Branch, Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 10408, South Korea.
Sungwook
S
Lee
Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, South Korea.
Boyoun
B
Park
D000818:Animals; D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D016384:Consensus Sequence; D016207:Cytokines / Q000235:genetics; D004405:Dysentery, Bacillary / Q000276:immunology; D006801:Humans; D053762:Interleukin-12 Subunit p40 / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D000072417:Protein Domains; D055503:Protein Multimerization; D021381:Protein Transport; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D012763:Shigella flexneri; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D015027:Zebrafish
D016207:Cytokines; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6; D016328:NF-kappa B; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C499012:Cnbp protein, mouse; C577686:interleukin-6, mouse