Inducible degradation of IkappaBalpha by the proteasome requires interaction with the F-box protein h-betaTrCP.
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.
Mesh Terms:
Cell Cycle Proteins, Cysteine Endopeptidases, DNA-Binding Proteins, GTP-Binding Proteins, Hela Cells, Humans, I-kappa B Proteins, Models, Chemical, Multienzyme Complexes, NF-kappa B, Peptide Synthases, Phosphorylation, Proteasome Endopeptidase Complex, S-Phase Kinase-Associated Proteins, SKP Cullin F-Box Protein Ligases, Serine, Transcription, Genetic, beta-Transducin Repeat-Containing Proteins
Cell Cycle Proteins, Cysteine Endopeptidases, DNA-Binding Proteins, GTP-Binding Proteins, Hela Cells, Humans, I-kappa B Proteins, Models, Chemical, Multienzyme Complexes, NF-kappa B, Peptide Synthases, Phosphorylation, Proteasome Endopeptidase Complex, S-Phase Kinase-Associated Proteins, SKP Cullin F-Box Protein Ligases, Serine, Transcription, Genetic, beta-Transducin Repeat-Containing Proteins
J. Biol. Chem.
Date: Mar. 19, 1999
PubMed ID: 10075690
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