c-rel regulation of IL-2 gene expression may be mediated through activation of AP-1

J Exp Med. 1996 Nov 1;184(5):1663-9. doi: 10.1084/jem.184.5.1663.

Abstract

T cell activation by antigen/MHC induces the expression of several genes critical to the immune response, including interleukin-2. T cells from mice deficient for the NF-kappa B family member c-rel cannot activate IL-2 gene expression. However, mutating the NF-kappa B site in the IL-2 promoter has only moderate effects. To investigate additional ways c-Rel could regulate IL-2 gene expression, we determined whether c-rel overexpression could increase the activity of other transcription factors involved in IL-2 promoter regulation: NF-AT, Oct/OAP (ARRE-1), and AP-1. In Jurkat TAg cells, overexpression of c-Rel increased AP-1 activation approximately 17-fold. Moreover, AP-1 activity stimulated by anti-TCR Abs or PMA/ionomycin was further increased by c-Rel overexpression. c-Rel overexpression did not affect NF-AT or ARRE-1 activity. Additionally, overexpression of c-Rel activated the nonconsensus AP-1 site from the IL-2 promoter (NF-IL-2B), although to a lesser extent, approximately sixfold. AP-1 activation required both the DNA binding and transactivation domains of c-Rel. Our results may provide an explanation for the effect on IL-2 gene activation in c-rel-deficient mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • DNA / metabolism
  • DNA-Binding Proteins / metabolism*
  • Genes, Reporter
  • Humans
  • Interleukin-2 / biosynthesis*
  • Interleukin-2 / genetics
  • Jurkat Cells
  • Mice
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Conformation
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-rel
  • T-Lymphocytes / immunology*
  • Transcription Factor AP-1 / metabolism*
  • Transcription Factors / metabolism
  • Up-Regulation*

Substances

  • DNA-Binding Proteins
  • Interleukin-2
  • NFATC Transcription Factors
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-rel
  • Transcription Factor AP-1
  • Transcription Factors
  • DNA