Transactivation by NF-IL6/LAP is enhanced by phosphorylation of its activation domain

• Published in: Nature (London) Vol. 364; no. 6437; pp. 544 - 547
• Main Authors: Trautwein, Christian, Caelles, Carme, van der Geer, Peter, Hunter, Tony, Karin, Michael, Chojkier, Mario
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 05-08-1993; Nature Publishing Group
• Subjects: Animals; Binding Sites; Biological and medical sciences; CCAAT-Enhancer-Binding Proteins; DNA - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Fundamental and applied biological sciences. Psychology; Fungal Proteins - genetics; Gene Expression Regulation; Genetics; Liver; Molecular and cellular biology; Molecular genetics; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Phosphopeptides - metabolism; Phosphorylation; Protein Kinase C - metabolism; Proteins; Rats; Saccharomyces cerevisiae Proteins; Serine - metabolism; Signal Transduction; Tetradecanoylphorbol Acetate - pharmacology; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription. Transcription factor. Splicing. Rna processing; Transcriptional Activation; Transfection; Tumor Cells, Cultured; Human; Signal transduction; Phosphorylation; Protein kinase C; Cell line; Hepatocyte; Structure activity relation; Transcription; Enzyme; DNA binding protein; Transcription factor
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/364544a0

One of the members of the bZIP family of transcriptional activators is NF-IL6/LAP (IL-6 DBP, C/EBP beta, CRP2). NF-IL6/LAP protein is highly expressed in liver nuclei, where it has been implicated as a master regulator of the acute-phase response, induced by interleukin-6 (IL-6) and other inflammatory mediators. Also, NF-IL6/LAP is involved in the activation of the IL-6 promoter in response to IL-1 and bacterial lipopolysaccharide. The control of NF-IL6/LAP expression and activity is complex and poorly understood. Under some conditions the NF-IL6/LAP gene is transcriptionally activated by IL-1 and lipopolysaccharide, whereas in other instances, its binding to cognate DNA sequences is enhanced by cytokines. Additionally, the ability of constitutively expressed NF-IL6/LAP to activate transcription is strongly augmented by IL-6, through an unknown signalling pathway. We now show that stimulation of the protein kinase C pathway increases the phosphorylation of Ser 105 within the activation domain of NF-IL6/LAP, and enhances its transcriptional efficacy.