β-TrCP Mediates the Signal-induced Ubiquitination of IκBβ*
- Chun Wu and
- Sankar Ghosh‡
- From the Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520
Abstract
We have examined the role of β-TrCP (β-transducin repeat-containing protein) in the ubiquitination and degradation of IκBβ, one of the two major IκB isoforms in mammalian cells. We demonstrate that β-TrCP interacts specifically with IκBβ, and such interaction is dependent on prior phosphorylation of IκBβ on serines 19 and 23. Interaction with β-TrCP is also necessary for ubiquitination of IκBβ upon stimulation of cells, and deletion of the F-box in β-TrCP abolishes its ability to ubiquitinate IκBβ. Therefore, these results indicate that β-TrCP plays a critical role in the activation of NF-κB by assembling the ubiquitin ligase complex for both phosphorylated IκBα and IκBβ.
Footnotes
-
↵* This work was supported by a grant from the National Institutes of Health (R01 AI33443) and the Howard Hughes Medical Institute.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
↵‡ To whom correspondence should be addressed. Tel.: 203-737-4419; Fax: 203-737-1764; E-mail: sankar.ghosh@yale.edu.
-
↵2 S. Ghosh, unpublished results.
-
↵3 C. Wu and S. Ghosh, unpublished observations.
- Abbreviations:
- IKK
-
IκB kinase complex
- β-TrCP
-
β-transducin repeat-containing protein
- SCF
-
Skp1-cullin-F-box
- HIV
-
human immunodeficiency virus
- RT-PCR
-
reverse transcriptase polymerase chain reaction
- TNF
-
tumor necrosis factor
- PAGE
-
polyacrylamide gel electrophoresis
- ECL
-
enhanced chemiluminescence
-
- Received May 12, 1999.
- Revision received August 5, 1999.
- The American Society for Biochemistry and Molecular Biology, Inc.
