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

Nature. 1993 Aug 5;364(6437):544-7. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding Sites
  • CCAAT-Enhancer-Binding Proteins
  • DNA / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Fungal Proteins / genetics
  • Gene Expression Regulation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Phosphopeptides / metabolism
  • Phosphorylation
  • Protein Kinase C / metabolism
  • Rats
  • Saccharomyces cerevisiae Proteins*
  • Serine / metabolism
  • Signal Transduction
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptional Activation*
  • Transfection
  • Tumor Cells, Cultured


  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins
  • Fungal Proteins
  • GAL4 protein, S cerevisiae
  • Nuclear Proteins
  • Phosphopeptides
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Serine
  • DNA
  • Protein Kinase C
  • Tetradecanoylphorbol Acetate