| First Author | Spencer E | Year | 1999 |
| Journal | Genes Dev | Volume | 13 |
| Issue | 3 | Pages | 284-94 |
| PubMed ID | 9990853 | Mgi Jnum | J:53039 |
| Mgi Id | MGI:1331223 | Doi | 10.1101/gad.13.3.284 |
| Citation | Spencer E, et al. (1999) Signal-induced ubiquitination of IkappaBalpha by the F-box protein Slimb/beta-TrCP. Genes Dev 13(3):284-94 |
| abstractText | 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. |
