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Originally published In Press as doi:10.1074/jbc.C200151200 on May 6, 2002

J. Biol. Chem., Vol. 277, Issue 25, 22111-22114, June 21, 2002
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ACCELERATED PUBLICATION
Genetic Evidence for the Essential Role of beta -Transducin Repeat-containing Protein in the Inducible Processing of NF-kappa B2/p100*

Abraham Fong and Shao-Cong SunDagger

From the Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033

Processing of the nfkappa b2 gene product p100 to generate p52 is an important step in NF-kappa B regulation. This step is regulated by a nonclassical NF-kappa B signaling pathway involving the NF-kappa B-inducing kinase (NIK). NIK induces p100 processing by triggering phosphorylation of specific C-terminal serines of p100. However, the downstream molecular events leading to p100 processing remain unclear. Here we show that NIK induced the physical recruitment of beta -transducin repeat-containing protein (beta -TrCP), a component of the SCF ubiquitin ligase complex, to p100. This event required the phosphorylation sites as well as the death domain of p100. Using the RNA interference technique, we demonstrated that beta -TrCP is essential for NIK-induced p100 ubiquitination and processing. Interestingly the constitutive processing of p100 mutants was independent of beta -TrCP. These results suggest that beta -TrCP is an essential component of NIK-induced p100 processing.

* This study was supported by United States Public Health Service Grant 1R01 AI45045 (to S.-C. S.).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.

Dagger To whom correspondence should be addressed: Dept. of Microbiology and Immunology, Pennsylvania State University College of Medicine, 500 University Dr., Hershey, PA 17033. Tel.: 717-531-4164; Fax: 717-531-6522; E-mail: sxs70@psu.edu.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.


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