PMID- 10066435
OWN - NLM
STAT- MEDLINE
DCOM- 19990413
LR  - 20161124
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 256
IP  - 1
DP  - 1999 Mar 5
TI  - IkappaBalpha ubiquitination is catalyzed by an SCF-like complex containing Skp1, 
      cullin-1, and two F-box/WD40-repeat proteins, betaTrCP1 and betaTrCP2.
PG  - 127-32
AB  - 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.
CI  - Copyright 1999 Academic Press.
FAU - Suzuki, H
AU  - Suzuki H
AD  - Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 21
      Miyukigaoka, Ibaraki, Tsukuba-shi, 305-8585, Japan.
FAU - Chiba, T
AU  - Chiba T
FAU - Kobayashi, M
AU  - Kobayashi M
FAU - Takeuchi, M
AU  - Takeuchi M
FAU - Suzuki, T
AU  - Suzuki T
FAU - Ichiyama, A
AU  - Ichiyama A
FAU - Ikenoue, T
AU  - Ikenoue T
FAU - Omata, M
AU  - Omata M
FAU - Furuichi, K
AU  - Furuichi K
FAU - Tanaka, K
AU  - Tanaka K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (BTRC protein, human)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Cullin 1)
RN  - 0 (Cullin Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (FBXW11 protein, human)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (NFKBIA protein, human)
RN  - 0 (S-Phase Kinase-Associated Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Ubiquitins)
RN  - 0 (beta-Transducin Repeat-Containing Proteins)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - EC 6.- (Ligases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Cell Cycle Proteins/*metabolism
MH  - *Cullin Proteins
MH  - DNA-Binding Proteins/*metabolism
MH  - GTP-Binding Proteins/genetics/*metabolism
MH  - Gene Library
MH  - HeLa Cells
MH  - Humans
MH  - *I-kappa B Proteins
MH  - Ligases/metabolism
MH  - Molecular Sequence Data
MH  - Multienzyme Complexes/metabolism
MH  - NF-KappaB Inhibitor alpha
MH  - Phosphorylation/drug effects
MH  - Precipitin Tests
MH  - Protein Binding/drug effects
MH  - S-Phase Kinase-Associated Proteins
MH  - Sequence Homology, Amino Acid
MH  - Signal Transduction
MH  - Transfection
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - Ubiquitin-Protein Ligases
MH  - Ubiquitins/*metabolism
MH  - beta-Transducin Repeat-Containing Proteins
EDAT- 1999/03/06 00:00
MHDA- 1999/03/06 00:01
CRDT- 1999/03/06 00:00
PHST- 1999/03/06 00:00 [pubmed]
PHST- 1999/03/06 00:01 [medline]
PHST- 1999/03/06 00:00 [entrez]
AID - S0006-291X(99)90289-9 [pii]
AID - 10.1006/bbrc.1999.0289 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 1999 Mar 5;256(1):127-32. doi:
      10.1006/bbrc.1999.0289.