The c-rel protooncogene product represses NF-kappa B p65-mediated transcriptional activation of the long terminal repeat of type 1 human immunodeficiency virus

Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):1023-7. doi: 10.1073/pnas.90.3.1023.


The long terminal repeat (LTR) of the type 1 human immunodeficiency virus (HIV-1) and the 5' regulatory region of the gene encoding the interleukin 2 receptor alpha subunit (IL-2R alpha) share functional kappa B enhancer elements involved in the regulation of these inducible transcription units during T-cell activation. These kappa B enhancer elements are recognized by a structurally related family of interactive proteins that includes p50, p65, and the product of the c-rel protooncogene (c-Rel). Recent biochemical studies have shown that p65 and p50 form the prototypical NF-kappa B complex, which is rapidly translocated from the cytoplasm to the nucleus during T-cell activation. This intracellular signaling complex potently stimulates kappa B-directed transcription from either the HIV-1 LTR or the IL-2R alpha promoter via the strong transactivation domain present in p65. We now demonstrate that nuclear expression of human c-Rel, which is induced by either phorbol ester or tumor necrosis factor alpha with delayed kinetics relative to p65, markedly represses p65-mediated activation of these transcription units. These inhibitory effects of c-Rel correlate with its DNA-binding activity but not with its ability to heterodimerize with p50, suggesting that c-Rel inhibition involves competition with p50/p65 for occupancy of the kappa B enhancer element. Together, these findings suggest that one function of c-Rel is as a physiologic repressor of the HIV-1 LTR and IL-2R alpha promoters, serving to efficiently counter the strong transcriptional activating effects of p65.

MeSH terms

  • Base Sequence
  • Chloramphenicol O-Acetyltransferase / genetics
  • DNA Mutational Analysis
  • Enhancer Elements, Genetic / genetics
  • Gene Expression Regulation, Viral / drug effects*
  • HIV Long Terminal Repeat / genetics*
  • HIV-1 / genetics*
  • Humans
  • Interleukin-2 / genetics
  • Molecular Sequence Data
  • NF-kappa B / metabolism*
  • Promoter Regions, Genetic / genetics
  • Proto-Oncogene Proteins / pharmacology*
  • Proto-Oncogene Proteins c-rel
  • Repressor Proteins / pharmacology*
  • T-Lymphocytes
  • Transcription, Genetic / drug effects
  • Transfection


  • Interleukin-2
  • NF-kappa B
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-rel
  • Repressor Proteins
  • Chloramphenicol O-Acetyltransferase