NESCA: a new NEMO/IKKgamma and TRAF6 interacting protein.
NEMO/IKKgamma is the essential regulatory subunit of the IkB Kinase (IKK) complex, required for the activation of Nuclear Factor kB (NF-kB) in many physiological processes such as inflammation, immunity, apoptosis, or development. NEMO works at a converging point of the NF-kB pathway as it interacts with upstream signaling molecules to orchestrate its activation. Here we report on the identification of a novel NEMO-interacting protein, NESCA, an adapter molecule previously shown to be involved in the NGF-pathway via the TrkA receptor. We demonstrated that NESCA and NEMO interact by their N-terminal region. Beside to NEMO, we revealed that NESCA directly associates to the E3 ubiquitin ligase TRAF6, which in turn catalyzes NESCA polyubiquitination. Finally, we demonstrated that NESCA overexpression strongly inhibits TRAF6-mediated polyubiquitination of NEMO. In summary, our results highlight that NESCA represents a novel missing link in the NEMO-mediated NF-kB activation pathway.
Napolitano
Gennaro
G
Institute of Genetics and Biophysics A Buzzati-Traverso, CNR, Naples, Italy.
Mirra
Serena
S
Monfregola
Jlenia
J
Lavorgna
Alfonso
A
Leonardi
Antonio
A
Ursini
Matilde Valeria
MV
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism*; D025821:Polyubiquitin / Q000378:metabolism; D011485:Protein Binding; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D054875:Ubiquitination
D048868:Adaptor Proteins, Signal Transducing; C491731:IKBKG protein, human; C410103:RUSC1 protein, human; D048029:TNF Receptor-Associated Factor 6; D025821:Polyubiquitin; D051550:I-kappa B Kinase