The same 50-kDa cellular protein binds to the negative regulatory elements of the interleukin 2 receptor alpha-chain gene and the human immunodeficiency virus type 1 long terminal repeat

Proc Natl Acad Sci U S A. 1989 Nov;86(21):8526-30. doi: 10.1073/pnas.86.21.8526.


We have investigated the biochemical basis for negative regulation of interleukin 2 receptor alpha-chain (IL-2R alpha) gene expression. Transient transfection studies employing internally deleted forms of the IL-2R alpha promoter localized a negative regulatory element (NRE) between nucleotides -400 and -368 relative to the major distal transcription start (cap) site. This 31-base-pair (bp) element is involved in the attenuation of both basal and inducible IL-2R alpha promoter activity. Comparison of this IL-2R alpha NRE with other known regulatory motifs revealed an 11-bp core element (TTCATCCCAGG) that was strikingly similar to a protein-binding domain within the long terminal repeat of the type 1 human immunodeficiency virus (HIV-1). This viral domain has been previously implicated in the negative control of HIV-1 gene expression. In vitro protein-DNA binding studies demonstrated that the same constitutively expressed approximately 50-kDa protein (SP-50) specifically bound to both the IL-2R alpha and HIV-1 NRE core elements. Mutation of the 11-bp IL-2R alpha NRE core element, which disrupted protein binding, significantly augmented basal as well as Tax protein- or phorbol ester-induced IL-2R alpha promoter activity in vivo, suggesting that SP-50 functions as a transcriptional silencer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Line
  • Chromosome Deletion
  • DNA / metabolism
  • DNA, Viral / metabolism
  • DNA-Binding Proteins / isolation & purification
  • DNA-Binding Proteins / metabolism*
  • Genes*
  • HIV-1 / genetics*
  • Humans
  • Macromolecular Substances
  • Molecular Weight
  • Mutation
  • Receptors, Interleukin-2 / genetics*
  • Regulatory Sequences, Nucleic Acid*
  • Repetitive Sequences, Nucleic Acid*
  • T-Lymphocytes / immunology


  • DNA, Viral
  • DNA-Binding Proteins
  • Macromolecular Substances
  • Receptors, Interleukin-2
  • DNA