Rel homology domain-containing transcription factors in the cnidarian Nematostella vectensis.
The Rel/NF-kappaB and NFAT families of transcription factors are related through an N-terminal DNA-binding domain called the Rel Homology domain (RHD). Neither the RHD nor the NF-kappaB pathway has been identified in a basal (i.e., nonbilaterian) animal phylum. Using genomic and cDNA databases, we have identified two RHD domain-containing proteins from the cnidarian Nematostella vectensis: an NF-kappaB-like protein (Nv-NF-kappaB) and an NFAT-like protein (Nv-NFAT). The gene structure and RHD predicted amino acid sequence of Nv-nfkb are similar to those of the vertebrate NF-kappaB p50/p52 proteins, whereas the sequence of Nv-NFAT allows only ambiguous assignment to the NFAT family. Nv-NF-kappaB lacks the C-terminal IkappaB-like sequences present in all other NF-kappaB proteins. There are, however, two IkappaB-like genes in Nematostella encoded by loci distinct from Nv-nfkb. The separate nfkb and ikb genes of Nematostella may reflect the ancestral metazoan condition, suggesting that a gene fusion event created the nfkb genes in Drosophila and vertebrates. Nematostella also has genes that encode upstream and downstream components of the vertebrate NF-kappaB signaling pathway. Upstream components include Toll- and tumor necrosis-like receptors and ligands, adaptor proteins (Trafs, Myd88), caspases, and a TBK-like kinase. Downstream components include the NF-kappaB coactivator protein Bcl-3 and several NF-kappaB target genes. These results demonstrate that RHD-containing transcription factors and associated pathways are evolutionarily more ancient than previously known. Moreover, they suggest models for the evolutionary diversification of the insect and vertebrate Rel/NF-kappaB/IkappaB and NFAT gene families and suggest that cnidarians possess an NF-kappaB-regulated developmental or stress response pathway.
Sullivan
James C
JC
Department of Biology, Boston University, 5 Cummington Street, Boston, MA 02215, USA.
Kalaitzidis
Demetrios
D
Gilmore
Thomas D
TD
Finnerty
John R
JR
D000595:Amino Acid Sequence; D000818:Animals; D003063:Cnidaria / Q000235:genetics*; D020672:I-kappa B Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000235:genetics; D050778:NFATC Transcription Factors / Q000235:genetics; D020572:Oncogene Proteins v-rel / Q000737:chemistry* / Q000235:genetics; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*
D020672:I-kappa B Proteins; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D020572:Oncogene Proteins v-rel; D014157:Transcription Factors