β-TrCP mediates the signal-induced ubiquitination of IκBβ

We have examined the role of beta-TrCP (beta-transducin repeat-containing protein) in the ubiquitination and degradation of I kappa B beta, one of the two major I kappa B isoforms in mammalian cells. We demonstrate that beta-TrCP interacts specifically with I kappa B beta, and such interaction is dependent on prior phosphorylation of I kappa B beta on serines 19 and 23. Interaction with beta-TrCP is also necessary for ubiquitination of I kappa B beta upon stimulation of cells, and deletion of the F-box in beta-TrCP abolishes its ability to ubiquitinate I kappa B beta. Therefore, these results indicate that beta-TrCP plays a critical role in the activation of NF-kappa B by assembling the ubiquitin ligase complex for both phosphorylated I kappa B alpha and I kappa B beta.