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Signal-induced site-specific phosphorylation targets I kappa B alpha to the ubiquitin-proteasome pathway.

The transcription factor NF-kappa B is sequestered in the cytoplasm by the inhibitor protein I kappa B alpha. Extracellular inducers of NF-kappa B activate signal transduction pathways that result in the phosphorylation and subsequent degradation of I kappa B alpha. At present, the link between phosphorylation of I kappa B alpha and its degradation is not understood. In this report we provide evidence that phosphorylation of serine residues 32 and 36 of I kappa B alpha targets the protein to the ubiquitin-proteasome pathway. I kappa B alpha is ubiquitinated in vivo and in vitro following phosphorylation, and mutations that abolish phosphorylation and degradation of I kappa B alpha in vivo prevent ubiquitination in vitro. Ubiquitinated I kappa B alpha remains associated with NF-kappa B, and the bound I kappa B alpha is degraded by the 26S proteasome. Thus, ubiquitination provides a mechanistic link between phosphorylation and degradation of I kappa B alpha.

Pubmed ID: 7628694


  • Chen Z
  • Hagler J
  • Palombella VJ
  • Melandri F
  • Scherer D
  • Ballard D
  • Maniatis T


Genes & development

Publication Data

July 1, 1995

Associated Grants


Mesh Terms

  • Cysteine Endopeptidases
  • DNA-Binding Proteins
  • HeLa Cells
  • Humans
  • I-kappa B Proteins
  • Kinetics
  • Leupeptins
  • Multienzyme Complexes
  • Mutagenesis, Site-Directed
  • NF-kappa B
  • Oxazoles
  • Phosphoprotein Phosphatases
  • Phosphorylation
  • Phosphoserine
  • Proteasome Endopeptidase Complex
  • Protein Biosynthesis
  • Recombinant Proteins
  • Ubiquitins