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Papers In Press, published online ahead of print May 6, 2002
Microbiology and Immunology, Penn State University College of Medicine, Hershey, PA 17033
Corresponding Author: sxs70{at}psu.edu
Processing of the nfkb2 gene product p100 to generate p52 is an important step in NF-kB regulation. This step is regulated by a nonclassical NF-kB signaling pathway involving the NF-kB 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 induces the physical recruitment of beta-transducin repeat-containing protein (b-TrCP), a component of the SCF ubiquitin ligase complex, to p100. This event requires the phosphorylation sites as well as the death domain of p100. Using the RNA interference (RNAi) technique, we demonstrate that b-TrCP is essential for NIK-induced p100 ubiquitination and processing. Interestingly, the constitutive processing of p100 mutants is independent of b-TrCP. These results suggest that b-TrCP is an essential component of NIK-induced p100 processing.
J. Biol. Chem, 10.1074/jbc.C200151200
Submitted on March 14, 2002
Revised on May 2, 2002
Accepted on May 3, 2002
Genetic evidence for the essential role of beta-transducin repeat-containing protein in the inducible processing of NF-kB2/p100
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