Signal-induced ubiquitination of IκBα by the F-box protein Slimb/β- TrCP

Erika Spencer, Jin Jiang, Zhijian J. Chen

Research output: Contribution to journalArticlepeer-review

373 Scopus citations


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

Original languageEnglish (US)
Pages (from-to)284-294
Number of pages11
JournalGenes and Development
Issue number3
StatePublished - Feb 1 1999


  • IκB
  • NF-κB
  • Phosphorylation
  • SCF
  • Slimb
  • Ubiquitin
  • β-TrCP

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology


Dive into the research topics of 'Signal-induced ubiquitination of IκBα by the F-box protein Slimb/β- TrCP'. Together they form a unique fingerprint.

Cite this