Please use this identifier to cite or link to this item: https://doi.org/10.1073/pnas.0507044103
DC FieldValue
dc.titleEvidence for the ancient origin of the NF-κB/IκB cascade: Its archaic role in pathogen infection and immunity
dc.contributor.authorWang, X.W.
dc.contributor.authorTan, N.S.
dc.contributor.authorBow Ho
dc.contributor.authorDing, J.L.
dc.date.accessioned2014-10-27T08:27:50Z
dc.date.available2014-10-27T08:27:50Z
dc.date.issued2006-03-14
dc.identifier.citationWang, X.W., Tan, N.S., Bow Ho, Ding, J.L. (2006-03-14). Evidence for the ancient origin of the NF-κB/IκB cascade: Its archaic role in pathogen infection and immunity. Proceedings of the National Academy of Sciences of the United States of America 103 (11) : 4204-4209. ScholarBank@NUS Repository. https://doi.org/10.1073/pnas.0507044103
dc.identifier.issn00278424
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/100618
dc.description.abstractThe evolutionary conservation of the NF-κB transcription factors, from Drosophila to humans, underscores its pivotal role in immune response. Unexpectedly, the canonical NF-κB signaling pathway is not functional in the immune system of Caenorhabditis elegans. Therefore, the ancient origin of the NF-κB signaling pathway is still unknown. Here, we report the discovery and characterization of a primitive and functional NF-κB/IκB pathway in the immune defense of a "living fossil," the horseshoe crab, Carcinoscorpius rotundicauda. The ancient NF-κB/IκB homologues, CrNFκB, CrRelish, and CrIκB, share numerous signature motifs with their vertebrate orthologues. CrNFκB recognizes both horseshoe crab and mammalian κB response elements. CrIκB interacts with CrNFκB and inhibits its nuclear translocation and DNA-binding activity. The activation of the CrNFκB is autoregulated by a feedback mechanism mediated by CrIκB, the natural inhibitor of CrNFκB. We further show that Gram-negative bacteria infection causes rapid degradation of CrIκB and nuclear translocation of CrNFκB. Infection also leads to an increase in the κB-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-κB/IκB 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. © 2006 by The National Academy of Sciences of the USA.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1073/pnas.0507044103
dc.sourceScopus
dc.subjectConservation and coevolution
dc.subjectHorseshoe crab
dc.subjectInfection and immune response
dc.subjectTranscriptional control
dc.typeArticle
dc.contributor.departmentBIOLOGICAL SCIENCES
dc.description.doi10.1073/pnas.0507044103
dc.description.sourcetitleProceedings of the National Academy of Sciences of the United States of America
dc.description.volume103
dc.description.issue11
dc.description.page4204-4209
dc.description.codenPNASA
dc.identifier.isiut000236429300050
dc.published.statePublished
Appears in Collections:Staff Publications

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