ArticleProceedings of the National Academy of Sciences of the United States of America2006
Evidence for the ancient origin of the NF-kappaB/IkappaB cascade: its archaic role in pathogen infection and immunity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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26 citing papers in PubMed, 94 citations in OpenAlex.
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- Immune Responses to Gram-Negative Bacteria in Hemolymph of the Chinese Horseshoe Crab,Frontiers in immunology · 2020Article
- Immunity-related genes and signaling pathways under hypoxic stresses in Haliotis diversicolor: a transcriptome analysis.Scientific reports · 2019Article
- Conservation and Divergence of p53 Oscillation Dynamics across Species.Cell systems · 2017Article
- Primate lentiviruses use at least three alternative strategies to suppress NF-κB-mediated immune activation.PLoS pathogens · 2017Article
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- Comparative Genomics Reveals the Origins and Diversity of Arthropod Immune Systems.Molecular biology and evolution · 2015Article
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- Identification and characterization of five transcription factors that are associated with evolutionarily conserved immune signaling pathways in the schistosome-transmitting snail Biomphalaria glabrata.Molecular immunology · 2011Article
- C-type natriuretic peptide modulates quorum sensing molecule and toxin production in Pseudomonas aeruginosa.Microbiology (Reading, England) · 2011Article
- Parallel evolution of nitric oxide signaling: diversity of synthesis and memory pathways.Frontiers in bioscience (Landmark edition) · 2011Review
- Modulation of NF-κB signalling by microbial pathogens.Nature reviews. Microbiology · 2011Review
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- A vaccinia virus deletion mutant reveals the presence of additional inhibitors of NF-kappaB.Journal of virology · 2011Article
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4 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
The evolutionary conservation of the NF-kappaB transcription factors, from Drosophila to humans, underscores its pivotal role in immune response. Unexpectedly, the canonical NF-kappaB signaling pathway is not functional in the immune system of Caenorhabditis elegans. Therefore, the ancient origin of the NF-kappaB signaling pathway is still unknown. Here, we report the discovery and characterization of a primitive and functional NF-kappaB/IkappaB pathway in the immune defense of a "living fossil," the horseshoe crab, Carcinoscorpius rotundicauda. The ancient NF-kappaB/IkappaB homologues, CrNFkappaB, CrRelish, and CrIkappaB, share numerous signature motifs with their vertebrate orthologues. CrNFkappaB recognizes both horseshoe crab and mammalian kappaB response elements. CrIkappaB interacts with CrNFkappaB and inhibits its nuclear translocation and DNA-binding activity. The activation of the CrNFkappaB is autoregulated by a feedback mechanism mediated by CrIkappaB, the natural inhibitor of CrNFkappaB. We further show that Gram-negative bacteria infection causes rapid degradation of CrIkappaB and nuclear translocation of CrNFkappaB. Infection also leads to an increase in the kappaB-binding activity and up-regulation of immune-related gene expression, like inducible nitric oxide synthase and Factor C, an LPS-activated serine protease. Altogether, our study shows that, although absent in C. elegans, the NF-kappaB/IkappaB signaling cascade remains well conserved from horseshoe crab to humans, playing an archaic but fundamental role in regulating the expression of critical immune defense molecules.
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