CSN3 interacts with IKKgamma and inhibits TNF- but not IL-1-induced NF-kappaB activation.
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Hong X, Xu L, Li X, Zhai Z, Shu H
CSN3 interacts with IKKgamma and inhibits TNF- but not IL-1-induced NF-kappaB activation.
FEBS Lett. 2001 Jun 15;499(1-2):133-6.
- PubMed ID
- 11418127 [ View in PubMed]
- Abstract
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.