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.
Oukka
Mohamed
M
Department of Immunology and Infectious Diseases, Harvard School of Public Health, 651 Huntington Avenue, FXB-2, Boston, MA 02115, USA.
Kim
Sean T
ST
Lugo
Geancarlo
G
Sun
Jenny
J
Wu
Lai-Chu
LC
Glimcher
Laurie H
LH
D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins; D006367:HeLa Cells; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D047992:TNF Receptor-Associated Factor 2; D014157:Transcription Factors / Q000235:genetics; D015533:Transcriptional Activation
D016207:Cytokines; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C084779:Hivep3 protein, mouse; D016328:NF-kappa B; D011506:Proteins; D018124:Receptors, Tumor Necrosis Factor; D047992:TNF Receptor-Associated Factor 2; D014157:Transcription Factors; C094066:shn protein, Drosophila