The p38 MAPK pathway is involved in the IL-2 induction of TNF-beta gene via the EBS element

Biochem Biophys Res Commun. 2001 Dec 21;289(5):979-86. doi: 10.1006/bbrc.2001.6069.


As an important cytokine of the immune system, interleukin-2 (IL-2) can induce the expression of various genes, one of which is the tumor necrosis factor-beta (TNF-beta). However, the induction mechanism of TNF-beta remains to be fully explored. We have previously shown JAK-STAT pathway mediates TNF-beta gene induction upon IL-2 stimulation through an upstream -200GAS element. In this study, we further demonstrated that there is another essential -130EBS element in TNF-beta gene promoter region. Using IL-2-dependent cell line BAF/BO3beta, we found that this -130EBS element can form a specific complex with nuclear protein, which contained a novel ETS transcription factor. Furthermore, using kinase inhibitors, we revealed that p38 MAP kinase is involved in the formation of -130EBS-protein complex and the subsequent transcriptional activation of TNF-beta gene in response to IL-2 stimulation. Taken together, our results suggested that the complicated IL-2 induction of TNF-beta gene expression requires not only the activation of JAK-STAT pathway on the -200GAS element, but also the cooperation of another signal pathway on the -130EBS element.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites / genetics
  • Cell Line
  • DNA / genetics
  • DNA / metabolism
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation / drug effects
  • Interleukin-2 / pharmacology*
  • Lymphotoxin-alpha / genetics*
  • Macromolecular Substances
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism*
  • Molecular Sequence Data
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism
  • Promoter Regions, Genetic / drug effects
  • Protein-Tyrosine Kinases / metabolism
  • Signal Transduction
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism
  • Transcriptional Activation
  • p38 Mitogen-Activated Protein Kinases


  • DNA-Binding Proteins
  • Interleukin-2
  • Lymphotoxin-alpha
  • Macromolecular Substances
  • Nuclear Proteins
  • Transcription Factors
  • DNA
  • Protein-Tyrosine Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases