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.
Wu
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Section of Immunobiology, Department of Molecular Biophysics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Ghosh
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D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D020672:I-kappa B Proteins; D010766:Phosphorylation; D011485:Protein Binding; D014452:Ubiquitins / Q000378:metabolism*; D044844:beta-Transducin Repeat-Containing Proteins
C471644:BTRC protein, human; D004268:DNA-Binding Proteins; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D014452:Ubiquitins; D044844:beta-Transducin Repeat-Containing Proteins; D019204:GTP-Binding Proteins