Cross-coupling of the NF-kappa B p65 and Fos/Jun Transcription Factors Produces Potentiated Biological Function

EMBO J. 1993 Oct;12(10):3879-91.

Abstract

NF-kappa B and AP-1 represent distinct mammalian transcription factors that target unique DNA enhancer elements. The heterodimeric NF-kappa B complex is typically composed of two DNA binding subunits, NF-kappa B p50 and NF-kappa B p65, which share structural homology with the c-rel proto-oncogene product. Similarly, the AP-1 transcription factor complex is comprised of dimers of the c-fos and c-jun proto-oncogene products or of closely related proteins. We now demonstrate that the bZIP regions of c-Fos and c-Jun are capable of physically interacting with NF-kappa B p65 through the Rel homology domain. This complex of NF-kappa B p65 and Jun or Fos exhibits enhanced DNA binding and biological function via both the kappa B and AP-1 response elements including synergistic activation of the 5' long terminal repeat of the human immunodeficiency virus type 1. These findings support a combinatorial mechanism of gene regulation involving the unexpected cross-coupling of two different classes of transcription factors to form novel protein complexes exhibiting potentiated biological activity.

Publication types

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

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Blotting, Western
  • Cytoplasm / metabolism
  • Electrophoresis, Polyacrylamide Gel
  • HIV Long Terminal Repeat*
  • HeLa Cells
  • Humans
  • Macromolecular Substances
  • Mice
  • Molecular Sequence Data
  • NF-kappa B / metabolism*
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-fos / metabolism*
  • Proto-Oncogene Proteins c-jun / metabolism*
  • Proto-Oncogene Proteins c-rel

Substances

  • Macromolecular Substances
  • NF-kappa B
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • Proto-Oncogene Proteins c-rel