CSN3 interacts with IKKgamma and inhibits TNF- but not IL-1-induced NF-kappaB activation.

The transcription factor nuclear factor kappaB (NF-kappaB) plays a pivotal role in immune and inflammatory responses. Activation of NF-kappaB requires the activity of IKK, a kinase complex that contains two catalytic subunits, IKKalpha and IKKbeta, and a regulatory subunit IKKgamma. To understand how IKK activity is regulated, we searched for ...
IKKgamma-interacting proteins by the yeast two-hybrid system. These screenings identified CSN3, a component of the COP9 signalsome, as a protein specifically interacting with IKKgamma. Overexpression of CSN3 inhibits NF-kappaB activation triggered by tumor necrosis factor (TNF), but not interleukin-1 (IL-1). Moreover, overexpression of CSN3 also inhibits NF-kappaB activation triggered by proteins involved in TNF signaling, including TNF-R1, TRAF2, RIP, and NIK, but not by TRAF6, a protein involved in IL-1 signaling. These data suggest that CSN3 is a specific negative regulator of TNF- but not IL-1-induced NF-kappaB activation pathways.
Mesh Terms:
Blotting, Western, Carrier Proteins, Cell Line, Down-Regulation, Genes, Reporter, Humans, I-kappa B Kinase, Interleukin-1, NF-kappa B, Precipitin Tests, Protein Binding, Protein-Serine-Threonine Kinases, Proteins, Receptor-Interacting Protein Serine-Threonine Kinases, Receptors, Tumor Necrosis Factor, Signal Transduction, TNF Receptor-Associated Factor 2, TNF Receptor-Associated Factor 6, Transcriptional Activation, Transfection, Tumor Necrosis Factor-alpha, Two-Hybrid System Techniques
FEBS Lett.
Date: Jun. 15, 2001
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