The Drosophila tumor necrosis factor receptor-associated factor-1 (DTRAF1)interacts with Pelle and regulates NF kappa B activity

A member of the tumor necrosis factor (TNF) receptor-associated factor (TRA F) family was identified in Drosophila. DTRAF1 contains 7 zinc finger domai ns followed by a TRAF domain, similar to mammalian TRAFs and other members of the family identified in data bases from Caenorhabditis elegans, Arabido psis, and Dictyostelium. Analysis of DTRAF1 binding to different members of the human TNF receptor family showed that this protein can interact throug h its TRAF domain with the p75 neurotrophin receptor and weakly with the ly mphotoxin-p receptor. DTRAF1 can also self-associate and binds to human TRA F1, TRAF2, and TRAF4. Interestingly, DTRAF1 interacts with human cIAP-1 and cIAP-2 but not with Drosophila DIAP-1 and -2. By itself, DTRAF1 did not in duce significant NF kappa B activation when overexpressed in mammalian cell s, although it specifically increased NF kappa B induction by TRAF6. In con trast, TRAF2-mediated NF kappa B induction was partially inhibited by DTRAF 1. Mutants of DTRAF1 lacking the N-terminal region inhibited NF kappa B ind uction by either TRAF2 or TRAF6. DTRAF1 specifically associated with the re gulatory N-terminal domain of Pelle, a Drosophila homolog of the human kina se interleukin-1 receptor-associated kinase (IRAK). Interestingly, though P elle and DTRAF1 individually were unable to induce NF kappa B in a human ce ll line, co-expression of Pelle and DTRAF1 resulted in significant NF kappa B activity. Interactions of DTRAF1 with human TRAF-, TNF receptor-, and IA P-family proteins imply strong evolutionary conservation of TRAF protein st ructure and function throughout Metazoan evolution.