C/EBP homologous protein (CHOP) up-regulates IL-6 transcription by trapping negative regulating NF-IL6 isoform.
Interleukin-6 (IL-6) production is up-regulated by several stimuli through the activation of transcription factors. We have previously demonstrated that CCAAT/enhancer binding protein homologous protein (CHOP) positively regulates IL-6 production at the transcriptional level in the human melanoma cell line A375. In this study, we provide evidence that CHOP up-regulates the IL-6 transcription without binding to the IL-6 promoter. CHOP dimerized more preferentially with an inhibitory isoform of nuclear factor for IL-6 expression (LIP (liver-enriched inhibitory protein)) than with a positively acting isoform (LAP, liver-enriched activator protein). These results indicate that CHOP plays an important role in IL-6 production without binding to its promoter, probably by trapping protein(s) such as LIP, which would otherwise inhibit IL-6 transcription.
Hattori
Takayuki
T
Department of Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Nagoya City University, Mizuho, Japan.
Ohoka
Nobumichi
N
Hayashi
Hidetoshi
H
Onozaki
Kikuo
K
D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics*; D008954:Models, Biological; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000378:metabolism; D020218:Response Elements; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D022782:CCAAT-Enhancer-Binding Protein-beta; D022762:CCAAT-Enhancer-Binding Proteins; C497249:DDIT3 protein, human; D015850:Interleukin-6; D020033:Protein Isoforms; D014157:Transcription Factors; D051742:Transcription Factor CHOP