IκBα Ubiquitination Is Catalyzed by an SCF-like Complex Containing Skp1, Cullin-1, and Two F-Box/WD40-Repeat Proteins, βTrCP1 and βTrCP2

Author： Suzuki H. Chiba T. Kobayashi M. Takeuchi M. Suzuki T. Ichiyama A. Ikenoue T. Omata M. Furuichi K. Tanaka K.

Publisher： Elsevier

ISSN： 0006-291X

Source： Biochemical and Biophysical Research Communications, Vol.256, Iss.1, 1999-03, pp. : 127-132

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Abstract

Destruction of the transcriptional inhibitor IκB by the ubiquitin (Ub) system is required for signal-dependent activation of the multifunctional transcriptional factor NF-κB, but details of this ubiquitination are largely unknown. We report here that the IκBα-ubiquitin ligase (IκBα-E3) is an SCF-like complex containing Skp1, cullin-1, and two homologous F-box/WD40-repeat proteins, βTrCP1 and βTrCP2. Intriguingly, all these components are cooperatively recruited to bind to a phosphorylated IκBα (pIκBα) produced by tumor necrosis factor-α (TNF-α) stimulation. IκBα-E3 bound to pIκBα catalyzed in vitro ubiquitination of pIκBα in the presence of ATP, Ub, and E1-activating and E2-conjugating enzymes. Forced expression of βTrCP1 and βTrCP2 resulted in dramatic augmentation of the in vitro polyubiquitination activity of IκBα-E3. These results indicate that the long-sought IκBα-E3 is an SCF-like complex consisting of multiple proteins which are coordinately assembled during phosphorylation of IκBα in response to external signals.