A mammalian homolog of Drosophila schnurri, KRC, regulates TNF receptor-driven responses and interacts with TRAF2.

The cytokine TNFalpha launches cascades of gene activation that control inflammation and apoptosis through NFkappaB and JNK/SAPK signal transduction pathways. Here we describe a function for the zinc finger transcription factor kappa recognition component (KRC) in regulating patterns of gene activation in response to proinflammatory stimuli. We demonstrate that KRC overexpression inhibits while antisense or dominant-negative KRC enhances NFkappaB-dependent transactivation and JNK phosphorylation and consequently, apoptosis and cytokine gene expression. The effect of KRC is mediated through its interaction with the adaptor protein TRAF2, which intersects both pathways. KRC is a hitherto unrecognized participant in the signal transduction pathway leading from the TNF receptor to gene activation and may play a critical role in inflammatory and apoptotic responses.