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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2000-2-29
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
28
pubmed:volume
275
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2877-84
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Homodimer of two F-box proteins betaTrCP1 or betaTrCP2 binds to IkappaBalpha for signal-dependent ubiquitination.
pubmed:affiliation
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Company Ltd., 21 Miyukigaoka, Tsukuba-shi, Ibaraki, 305-8585, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't