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dc.contributor.authorSullivan, James C.en_US
dc.contributor.authorWolenski, Francis S.en_US
dc.contributor.authorReitzel, Adam M.en_US
dc.contributor.authorFrench, Courtney E.en_US
dc.contributor.authorTraylor-Knowles, Nikkien_US
dc.contributor.authorGilmore, Thomas D.en_US
dc.contributor.authorFinnerty, John R.en_US
dc.date.accessioned2012-01-11T16:55:00Z
dc.date.available2012-01-11T16:55:00Z
dc.date.issued2009-10-6
dc.identifier.citationSullivan, James C., Francis S. Wolenski, Adam M. Reitzel, Courtney E. French, Nikki Traylor-Knowles, Thomas D. Gilmore, John R. Finnerty. "Two Alleles of NF-κB in the Sea Anemone Nematostella vectensis Are Widely Dispersed in Nature and Encode Proteins with Distinct Activities" PLoS ONE 4(10): e7311. (2009)
dc.identifier.issn1932-6203
dc.identifier.urihttps://hdl.handle.net/2144/3135
dc.description.abstractBACKGROUND. NF-κB is an evolutionarily conserved transcription factor that controls the expression of genes involved in many key organismal processes, including innate immunity, development, and stress responses. NF-κB proteins contain a highly conserved DNA-binding/dimerization domain called the Rel homology domain. METHODS/PRINCIPAL FINDINGS. We characterized two NF-κB alleles in the sea anemone Nematostella vectensis that differ at nineteen single-nucleotide polymorphisms (SNPs). Ten of these SNPs result in amino acid substitutions, including six within the Rel homology domain. Both alleles are found in natural populations of Nematostella. The relative abundance of the two NF-κB alleles differs between populations, and departures from Hardy-Weinberg equilibrium within populations indicate that the locus may be under selection. The proteins encoded by the two Nv-NF-κB alleles have different molecular properties, in part due to a Cys/Ser polymorphism at residue 67, which resides within the DNA recognition loop. In nearly all previously characterized NF-κB proteins, the analogous residue is fixed for Cys, and conversion of human RHD proteins from Cys to Ser at this site has been shown to increase DNA-binding ability and increase resistance to inhibition by thiol-reactive compounds. However, the naturally-occurring Nematostella variant with Cys at position 67 binds DNA with a higher affinity than the Ser variant. On the other hand, the Ser variant activates transcription in reporter gene assays more effectively, and it is more resistant to inhibition by a thiol-reactive compound. Reciprocal Cys<->Ser mutations at residue 67 of the native Nv-NF-κB proteins affect DNA binding as in human NF-κB proteins, e.g., a Cys->Ser mutation increases DNA binding of the native Cys variant. CONCLUSIONS/SIGNIFICANCE. These results are the first demonstration of a naturally occurring and functionally significant polymorphism in NF-κB in any species. The functional differences between these alleles and their uneven distribution in the wild suggest that different genotypes could be favored in different environments, perhaps environments that vary in their levels of peroxides or thiol-reactive compounds.en_US
dc.description.sponsorshipNational Institutes of Health (CA047763); National Science Foundation (FP-91656101-0); Environmental Protection Agency (F5E11155); Conservation International Marine Management Area Science Program; Boston University (SPRInG grant); Postdoctoral Scholar Program at the Woods Hole Oceanographic Institution; The Beacon Institute for Rivers and Estuaries; the J Seward Johnson Fund; Boston University (5 P42 ES07381)en_US
dc.language.isoen
dc.publisherPublic Library of Scienceen_US
dc.rightsSullivan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.titleTwo Alleles of NF-κB in the Sea Anemone Nematostella vectensis Are Widely Dispersed in Nature and Encode Proteins with Distinct Activitiesen_US
dc.typeArticleen_US
dc.identifier.doi10.1371/journal.pone.0007311
dc.identifier.pmid19806194
dc.identifier.pmcid2751831


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