PMID- 10644755
OWN - NLM
STAT- MEDLINE
DCOM- 20000229
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 275
IP  - 4
DP  - 2000 Jan 28
TI  - Homodimer of two F-box proteins betaTrCP1 or betaTrCP2 binds to IkappaBalpha for 
      signal-dependent ubiquitination.
PG  - 2877-84
AB  - We found previously that overexpression of an F-box protein betaTrCP1 and the
      structurally related betaTrCP2 augments ubiquitination of phosphorylated
      IkappaBalpha (pIkappaBalpha) induced by tumor necrosis factor-alpha (TNF-alpha), 
      but the relationship of the two homologous betaTrCP proteins remains unknown.
      Herein we reveal that deletion mutants of betaTrCP1 and betaTrCP2 lacking the
      F-box domain suppressed ubiquitination and destruction of pIkappaBalpha as well
      as transcriptional activation of NF-kappaB. The ectopically expressed betaTrCP1
      and betaTrCP2 formed both homodimer and heterodimer complexes without displaying 
      the trimer complex. Dimerization of betaTrCP1 and/or betaTrCP2 takes place at
      their conserved NH(2)-terminal regions, termed a "D-domain" (for dimerization
      domain), located upstream of the F-box domain. The D-domain was necessary and
      sufficient for the dimer formation. Intriguingly, the betaTrCP homodimer, but not
      the heterodimer, was selectively recruited to pIkappaBalpha induced by TNF-alpha.
      These results indicate that not only betaTrCP1 but also betaTrCP2 participates in
      the ubiquitination-dependent destruction of IkappaBalpha by forming
      SCF(betaTrCP1-betaTrCP1) and SCF(betaTrCP2-betaTrCP2) ubiquitin-ligase complexes.
FAU - Suzuki, H
AU  - Suzuki H
AD  - Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Company Ltd., 21
      Miyukigaoka, Tsukuba-shi, Ibaraki, 305-8585, Japan.
FAU - Chiba, T
AU  - Chiba T
FAU - Suzuki, T
AU  - Suzuki T
FAU - Fujita, T
AU  - Fujita T
FAU - Ikenoue, T
AU  - Ikenoue T
FAU - Omata, M
AU  - Omata M
FAU - Furuichi, K
AU  - Furuichi K
FAU - Shikama, H
AU  - Shikama H
FAU - Tanaka, K
AU  - Tanaka K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (BTRC protein, human)
RN  - 0 (DNA Primers)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (FBXW11 protein, human)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (NFKBIA protein, human)
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)
SB  - IM
MH  - Base Sequence
MH  - Cell Line
MH  - DNA Primers
MH  - DNA-Binding Proteins/*metabolism
MH  - Dimerization
MH  - GTP-Binding Proteins/genetics/*metabolism
MH  - Humans
MH  - Hydrolysis
MH  - *I-kappa B Proteins
MH  - Mutagenesis
MH  - NF-KappaB Inhibitor alpha
MH  - Protein Binding
MH  - Sequence Deletion
MH  - *Signal Transduction
MH  - Ubiquitin-Protein Ligases
MH  - Ubiquitins/*metabolism
MH  - beta-Transducin Repeat-Containing Proteins
EDAT- 2000/01/25 09:00
MHDA- 2000/03/04 09:00
CRDT- 2000/01/25 09:00
PHST- 2000/01/25 09:00 [pubmed]
PHST- 2000/03/04 09:00 [medline]
PHST- 2000/01/25 09:00 [entrez]
AID - 10.1074/jbc.275.4.2877 [doi]
PST - ppublish
SO  - J Biol Chem. 2000 Jan 28;275(4):2877-84. doi: 10.1074/jbc.275.4.2877.