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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

beta-TrCP mediates the signal- induced ubiquitination of IkappaBbeta.

We have examined the role of beta-TrCP (beta-transducin repeat-containing protein) in the ubiquitination and degradation of IkappaBbeta, one of the two major IkappaB isoforms in mammalian cells. We demonstrate that beta-TrCP interacts specifically with IkappaBbeta, and such interaction is dependent on prior phosphorylation of IkappaBbeta on serines 19 and 23. Interaction with beta-TrCP is also necessary for ubiquitination of IkappaBbeta upon stimulation of cells, and deletion of the F-box in beta-TrCP abolishes its ability to ubiquitinate IkappaBbeta. Therefore, these results indicate that beta-TrCP plays a critical role in the activation of NF-kappaB by assembling the ubiquitin ligase complex for both phosphorylated IkappaBalpha and IkappaBbeta.[1]


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