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PMID:9990853
| Citation |
Spencer, E, Jiang, J and Chen, ZJ (1999) Signal-induced ubiquitination of IkappaBalpha by the F-box protein Slimb/beta-TrCP. Genes Dev. 13:284-94 |
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| 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. |
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| Keywords |
Animals; Base Sequence; Cell Cycle Proteins; Cell Line, Transformed; DNA, Complementary; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Drosophila/embryology; Drosophila Proteins; Female; GTP-Binding Proteins/genetics; GTP-Binding Proteins/metabolism; Humans; I-kappa B Proteins; Insect Proteins; Ligases/metabolism; Male; Molecular Sequence Data; NF-kappa B/antagonists & inhibitors; NF-kappa B/metabolism; Nuclear Proteins/metabolism; Phosphoproteins/metabolism; Phosphorylation; Signal Transduction; Transcription Factors/metabolism; Twist Transcription Factor; Ubiquitin-Protein Ligases; Ubiquitins/metabolism; beta-Transducin Repeat-Containing Proteins |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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