title: Hydroid TNF-receptor-associated factor (TRAF) and its splice variant: a role in development.
abstract: TNF-receptor-associated factors (TRAFs) mediate signaling via tumor necrosis factor receptor (TNFR)/TLR molecules, playing a role in cellular processes such as growth, differentiation and apoptosis. They have been most studied in the immunological context. Within the animal kingdom, TRAFs have been characterized from vertebrates, flies and worms. We have cloned and characterized the first TRAF homologue from a member of the most basal eumetazoan phylum, the Cnidaria. The cnidarian TRAF, HyTRAF1, is a typical member of its family, containing one RING finger and five zinc finger domains in its N-terminal region, followed by a TRAF domain located at the C terminus. In addition to the full-length mRNA, the gene is alternatively spliced to create a shorter isoform, HyTRAF1a, with a deletion of 35 amino acids, resulting in a protein with only four zinc fingers. This is the first described TRAF alternative splicing in invertebrates. Whereas the full-length protein is expressed in most life stages of the animal, the short isoform is exclusively found at the larval and early metamorphic stages. This stage is characterized by extensive apoptosis, suggesting that HyTRAF1a mediates a proapoptotic c-jun N-terminal kinase (JNK) signaling, similar to the murine TRAF2A isoform. Based on neighbor joining analysis of TRAF molecules across the animal kingdom, we propose that the cnidarian TRAF interacts with TNFR, rather than with TLR. Our findings suggest that TNF signaling has evolved in the common ancestor to cnidarians and bilaterians and that it has been conserved in the entire animal kingdom.
authors.affiliation: Institute of Zoology, University of Heidelberg, INF 230, Heidelberg 69120, Germany.
authors.forename: Brahim
authors.initials: B
authors.lastname: Mali
authors.forename: Uri
authors.initials: U
authors.lastname: Frank
mesh_terms: D017398:Alternative Splicing; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D003063:Cnidaria / Q000196:embryology / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D019143:Evolution, Molecular; D007448:Invertebrates / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D007814:Larva; D008675:Metamorphosis, Biological; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000502:physiology; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013045:Species Specificity; D047990:TNF Receptor-Associated Factor 1; D014714:Vertebrates / Q000378:metabolism; D016335:Zinc Fingers / Q000235:genetics
chemical_list: D020033:Protein Isoforms; D011506:Proteins; D047990:TNF Receptor-Associated Factor 1; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases