NF-kappa B controls expression of inhibitor I kappa B alpha: evidence for an inducible autoregulatory pathway

Science. 1993 Mar 26;259(5103):1912-5. doi: 10.1126/science.8096091.


The eukaryotic transcription factor nuclear factor-kappa B (NF-kappa B) participates in many parts of the genetic program mediating T lymphocyte activation and growth. Nuclear expression of NF-kappa B occurs after its induced dissociation from its cytoplasmic inhibitor I kappa B alpha. Phorbol ester and tumor necrosis factor-alpha induction of nuclear NF-kappa B is associated with both the degradation of performed I kappa B alpha and the activation of I kappa B alpha gene expression. Transfection studies indicate that the I kappa B alpha gene is specifically induced by the 65-kilodalton transactivating subunit of NF-kappa B. Association of the newly synthesized I kappa B alpha with p65 restores intracellular inhibition of NF-kappa B DNA binding activity and prolongs the survival of this labile inhibitor. Together, these results show that NF-kappa B controls the expression of I kappa B alpha by means of an inducible autoregulatory pathway.

Publication types

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

MeSH terms

  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Line
  • Cell Nucleus / metabolism
  • Cycloheximide / pharmacology
  • Cytoplasm / metabolism
  • DNA / metabolism
  • DNA-Binding Proteins / genetics*
  • Gene Expression Regulation*
  • Humans
  • I-kappa B Proteins*
  • Immunoblotting
  • Kinetics
  • Molecular Weight
  • Mutagenesis
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / genetics
  • NF-kappa B / physiology*
  • RNA, Messenger / biosynthesis
  • Tetradecanoylphorbol Acetate / pharmacology
  • Trans-Activators / pharmacology
  • Transfection
  • Tumor Necrosis Factor-alpha / pharmacology


  • DNA-Binding Proteins
  • I kappa B beta protein
  • I-kappa B Proteins
  • NF-kappa B
  • RNA, Messenger
  • Trans-Activators
  • Tumor Necrosis Factor-alpha
  • DNA
  • Cycloheximide
  • Tetradecanoylphorbol Acetate