IkappaBalpha ubiquitination is catalyzed by an SCF-like complex containing Skp1, cullin-1, and two F-box/WD40-repeat proteins, betaTrCP1 and betaTrCP2.

Destruction of the transcriptional inhibitor IkappaB by the ubiquitin (Ub) system is required for signal-dependent activation of the multifunctional transcriptional factor NF-kappaB, but details of this ubiquitination are largely unknown. We report here that the IkappaBalpha-ubiquitin ligase (IkappaBalpha-E3) is an SCF-like complex containing Skp1, cullin-1, and two homologous F-box/WD40-repeat proteins, ...
betaTrCP1 and betaTrCP2. Intriguingly, all these components are cooperatively recruited to bind to a phosphorylated IkappaBalpha (pIkappaBalpha) produced by tumor necrosis factor-alpha (TNF-alpha) stimulation. IkappaBalpha-E3 bound to pIkappaBalpha catalyzed in vitro ubiquitination of pIkappaBalpha in the presence of ATP, Ub, and E1-activating and E2-conjugating enzymes. Forced expression of betaTrCP1 and betaTrCP2 resulted in dramatic augmentation of the in vitro polyubiquitination activity of IkappaBalpha-E3. These results indicate that the long-sought IkappaBalpha-E3 is an SCF-like complex consisting of multiple proteins which are coordinately assembled during phosphorylation of IkappaBalpha in response to external signals.
Mesh Terms:
Amino Acid Sequence, Cell Cycle Proteins, Cullin Proteins, DNA-Binding Proteins, GTP-Binding Proteins, Gene Library, Hela Cells, Humans, I-kappa B Proteins, Ligases, Molecular Sequence Data, Multienzyme Complexes, Phosphorylation, Precipitin Tests, Protein Binding, S-Phase Kinase-Associated Proteins, Sequence Homology, Amino Acid, Signal Transduction, Transfection, Tumor Necrosis Factor-alpha, Ubiquitin-Protein Ligases, Ubiquitins, beta-Transducin Repeat-Containing Proteins
Biochem. Biophys. Res. Commun.
Date: Mar. 05, 1999
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