IκBα Ubiquitination Is Catalyzed by an SCF-like Complex Containing Skp1, Cullin-1, and Two F-Box/WD40-Repeat Proteins, βTrCP1 and βTrCP2
Copyright policy )IκBα Ubiquitination Is Catalyzed by an SCF-like Complex Containing Skp1, Cullin-1, and Two F-Box/WD40-Repeat Proteins, βTrCP1 and βTrCP2
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.
Sequence Homology, Amino Acid, Molecular Sequence Data, Cell Cycle Proteins, Cullin Proteins, Transfection, Precipitin Tests, DNA-Binding Proteins, Ligases, NF-KappaB Inhibitor alpha, GTP-Binding Proteins, Multienzyme Complexes, Humans, I-kappa B Proteins, Amino Acid Sequence, Phosphorylation, S-Phase Kinase-Associated Proteins, Gene Library, HeLa Cells, Protein Binding, Signal Transduction
Sequence Homology, Amino Acid, Molecular Sequence Data, Cell Cycle Proteins, Cullin Proteins, Transfection, Precipitin Tests, DNA-Binding Proteins, Ligases, NF-KappaB Inhibitor alpha, GTP-Binding Proteins, Multienzyme Complexes, Humans, I-kappa B Proteins, Amino Acid Sequence, Phosphorylation, S-Phase Kinase-Associated Proteins, Gene Library, HeLa Cells, Protein Binding, Signal Transduction
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).108 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 1%
Citations provided by BIP!Popularity provided by BIP!