IL-6-inducible Complexes on an IL-6 Response Element of the junB Promoter Contain Stat3 and 36 kDa CRE-like Site Binding Protein(s)

Oncogene. 1996 Feb 1;12(3):547-54.

Abstract

The junB gene is one of immediate-early genes whose expression are regulated by a variety of extracellular stimuli and play important roles in cellular responses to the given stimuli. Interleukin-6 (IL-6) activates the junB promoter through an IL-6 response element, JRE-IL6, that is composed of two cooperative DNA motifs, a low affinity Stat-binding site overlapping with an Ets-binding site (JEBS) and a cAMP responsive element (CRE)-like site. This element is a target for the Jak-Stat signal transduction pathway. We showed that IL-6 induced novel complexes on JRE-IL6, termed JRE-IL6-BC1 and 2, which contained Stat3 but migrated more slowly than the complexes containing homo- or heterodimer of Stat3 and Stat1 in gel shift assays. These slow-migrating JRE-IL6-BCs appeared to contain CRE-like site binding proteins besides Stat3, since the formation of JRE-IL6-BCs required both the JEBS and CRE-like site of JRE-IL6 and oligonucleotides containing the CRE-like site or somatostatin CRE efficiently competed with JRE-IL6 for making JRE-IL6-BCs. The formation of the complexes correlated well with the responsiveness of JRE-IL6 to IL-6 signals. U.v.-cross linking study revealed that JRE-IL6 bound a 90 kDa protein, corresponding to Stat3, and a 36 kDa protein, most likely a CRE-like site binding protein(s). Furthermore, we showed that the IL-6/interferon gamma (IFN gamma) response element in the IRF-1 promoter (IR/IRF-1), which contains a Stat-binding site and an adjacent CRE-like site, also makes IL-6-induced binding complexes similar to JRE-IL6-BCs.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Binding Sites
  • Carcinoma, Hepatocellular
  • Cell Line
  • Cyclic AMP Response Element-Binding Protein / isolation & purification
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • DNA-Binding Proteins / isolation & purification
  • DNA-Binding Proteins / metabolism*
  • Genes, jun*
  • Humans
  • Interleukin-6 / pharmacology*
  • Liver Neoplasms
  • Macromolecular Substances
  • Molecular Sequence Data
  • Promoter Regions, Genetic*
  • STAT3 Transcription Factor
  • Signal Transduction
  • Trans-Activators / isolation & purification
  • Trans-Activators / metabolism*
  • Tumor Cells, Cultured

Substances

  • Cyclic AMP Response Element-Binding Protein
  • DNA-Binding Proteins
  • Interleukin-6
  • Macromolecular Substances
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Trans-Activators