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PMID: 9990853 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Signal-induced ubiquitination of IkappaBalpha by the F-box protein Slimb/beta-TrCP.

Genes & development ·Vol. 13 ·No. 3 ·1999-02-01 ·Pages 284-94

Spencer E, Jiang J, Chen ZJ

Abstract

Signal-induced phosphorylation of IkappaBalpha targets this inhibitor of NF-kappaB for ubiquitination and subsequent degradation, thus allowing NF-kappaB to enter the nucleus to turn on its target genes. We report here the identification of an IkappaB-ubiquitin (Ub) ligase complex containing the F-box/WD40-repeat protein, beta-TrCP, a vertebrate homolog of Drosophila Slimb. beta-TrCP binds to IkappaBalpha only when the latter is specifically phosphorylated by an IkappaB kinase complex. Moreover, immunopurified beta-TrCP ubiquitinates phosphorylated IkappaBalpha at specific lysines in the presence of Ub-activating (E1) and -conjugating (Ubch5) enzymes. A beta-TrCP mutant lacking the F-box inhibits the signal-induced degradation of IkappaBalpha and subsequent activation of NF-kappaB-dependent transcription. Furthermore, Drosophila embryos deficient in slimb fail to activate twist and snail, two genes known to be regulated by the NF-kappaB homolog, Dorsal. These biochemical and genetic data strongly suggest that Slimb/beta-TrCP is the specificity determinant for the signal-induced ubiquitination of IkappaBalpha.

MeSH Terms
Animals Base Sequence Cell Cycle Proteins Cell Line, Transformed DNA, Complementary DNA-Binding Proteins/genetics,metabolism Drosophila/embryology Drosophila Proteins Female GTP-Binding Proteins/genetics,metabolism Humans I-kappa B Proteins Insect Proteins Ligases/metabolism Male Molecular Sequence Data NF-KappaB Inhibitor alpha NF-kappa B/antagonists & inhibitors,metabolism Nuclear Proteins/metabolism Phosphoproteins/metabolism Phosphorylation Signal Transduction Snail Family Transcription Factors Transcription Factors/metabolism Twist-Related Protein 1 Ubiquitin-Protein Ligases Ubiquitins/metabolism beta-Transducin Repeat-Containing Proteins
Chemicals
BTRC protein, human Cell Cycle Proteins DNA, Complementary DNA-Binding Proteins Drosophila Proteins I-kappa B Proteins Insect Proteins NF-kappa B NFKBIA protein, human Nuclear Proteins Phosphoproteins Snail Family Transcription Factors TWIST1 protein, human Transcription Factors Twi protein, Drosophila Twist-Related Protein 1 Ubiquitins beta-Transducin Repeat-Containing Proteins dl protein, Drosophila slmb protein, Drosophila sna protein, Drosophila NF-KappaB Inhibitor alpha Ubiquitin-Protein Ligases GTP-Binding Proteins Ligases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Spencer E
Department of Molecular Biology and Oncology, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9148 USA.
Jiang J
Chen Z J
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.13.3.284
Published
1999-02-01
Pages
284-94
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC316434
Subset
IM
Databases
GENBANK
AF112979
External Links
PubMed source DOI: 10.1101/gad.13.3.284 PMC Full Text View journal details
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