The CD40L promoter contains nuclear factor of activated T cells-binding motifs which require AP-1 binding for activation of transcription

J Biol Chem. 1996 Feb 16;271(7):3763-70. doi: 10.1074/jbc.271.7.3763.

Abstract

Four nuclear factor of activated T cells (NF-AT) binding motifs were found in the murine CD40 ligand promoter. Electrophoretic mobility shift assays using 18-base pair (bp) long oligonucleotides corresponding to the proximal site and nuclear extracts from activated T cells revealed two complexes which were inhibited by cyclosporin A and contained NF-ATc and NF-ATp. Neither complex contained AP-1 proteins. Multimers of the 18-bp oligonucleotides were not active in transient transfection assays using luciferase reporter gene constructs. In contrast, a 30-bp long oligonucleotide bound AP-1 proteins in addition to NF-AT proteins and its multimers strongly induced luciferase gene expression. These results suggested that NF-AT proteins play an important role in the expression of the CD40L gene and that their transcriptional activity requires AP-1 binding.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • CD40 Antigens / immunology
  • CD40 Ligand
  • Cell Line
  • Cell Nucleus / metabolism
  • Consensus Sequence
  • DNA-Binding Proteins / metabolism*
  • Flow Cytometry
  • Interleukin-2 / genetics
  • Luciferases / biosynthesis
  • Lymphocyte Activation
  • Membrane Glycoproteins / biosynthesis*
  • Membrane Glycoproteins / genetics*
  • Mice
  • Molecular Sequence Data
  • NFATC Transcription Factors
  • Nuclear Proteins / metabolism
  • Oligodeoxyribonucleotides
  • Promoter Regions, Genetic*
  • Recombinant Proteins / biosynthesis
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Transcription Factor AP-1 / metabolism*
  • Transcription Factors / metabolism*
  • Transcriptional Activation*
  • Tumor Cells, Cultured

Substances

  • CD40 Antigens
  • DNA-Binding Proteins
  • Interleukin-2
  • Membrane Glycoproteins
  • NFATC Transcription Factors
  • Nuclear Proteins
  • Oligodeoxyribonucleotides
  • Recombinant Proteins
  • Transcription Factor AP-1
  • Transcription Factors
  • CD40 Ligand
  • Luciferases