How NF-kappaB is activated: the role of the IkappaB kinase (IKK) complex

Oncogene. 1999 Nov 22;18(49):6867-74. doi: 10.1038/sj.onc.1203219.

Abstract

Rel/NF-kappaB transcription factors are primarily regulated by association with inhibitor IkappaB proteins. Thus, in most cells NF-kappaB exists in the cytoplasm in an inactive complex bound to IkappaB. Most agents that activate NF-kappaB do so through a common pathway based on phosphorylation-induced, proteasome-mediated degradation of IkappaB. The key regulatory step in this pathway involves activation of a high molecular weight IkappaB kinase (IKK) complex, whose catalysis is generally carried out by a heterodimeric kinase consisting of IKKalpha and IKKbeta subunits. This review describes the identification of proteins in the IKK complex, and the regulation and physiological functions of IKK.

Publication types

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

MeSH terms

  • Animals
  • Humans
  • I-kappa B Kinase
  • NF-kappa B / metabolism*
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / physiology*
  • Proto-Oncogene Proteins / metabolism
  • Transcription Factor RelB
  • Transcription Factors / metabolism

Substances

  • NF-kappa B
  • Proto-Oncogene Proteins
  • RELB protein, human
  • Transcription Factors
  • Transcription Factor RelB
  • Protein-Serine-Threonine Kinases
  • CHUK protein, human
  • I-kappa B Kinase
  • IKBKB protein, human
  • IKBKE protein, human