Inducible degradation of IkappaBalpha by the proteasome requires interaction with the F-box protein h-betaTrCP

M Kroll, F Margottin, A Kohl, P Renard, H Durand, J P Concordet, F Bachelerie, F Arenzana-Seisdedos, R Benarous

Research output: Contribution to journalArticlepeer-review


Activation of NF-kappaB transcription factors requires phosphorylation and ubiquitin-proteasome-dependent degradation of IkappaB proteins. We provide evidence that a human F-box protein, h-betaTrCP, a component of Skp1-Cullin-F-box protein (SCF) complexes, a new class of E3 ubiquitin ligases, is essential for inducible degradation of IkappaBalpha. betaTrCP associates with Ser32-Ser36 phosphorylated, but not with unmodified IkappaBalpha or Ser32-Ser36 phosphorylation-deficient mutants. Expression of a F-box-deleted betaTrCP inhibits IkappaBalpha degradation, promotes accumulation of phosphorylated Ser32-Ser36 IkappaBalpha, and prevents NF-kappaB-dependent transcription. Our findings indicate that betaTrCP is the adaptor protein required for IkappaBalpha recognition by the SCFbetaTrCP E3 complex that ubiquitinates IkappaBalpha and makes it a substrate for the proteasome.
Original languageEnglish
Pages (from-to)7941-5
Number of pages5
JournalThe Journal of Biological Chemistry
Issue number12
Publication statusPublished - 19 Mar 1999


  • beta-Transducin Repeat-Containing Proteins
  • NF-kappa B
  • Cell Cycle Proteins
  • HeLa Cells
  • Peptide Synthases
  • DNA-Binding Proteins
  • Humans
  • Transcription, Genetic
  • GTP-Binding Proteins
  • S-Phase Kinase-Associated Proteins
  • SKP Cullin F-Box Protein Ligases
  • Multienzyme Complexes
  • Phosphorylation
  • Cysteine Endopeptidases
  • I-kappa B Proteins
  • Proteasome Endopeptidase Complex
  • Models, Chemical
  • Serine


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