The Drosophila tumor necrosis factor receptor-associated factor-1 (DTRAF1) interacts with Pelle and regulates NFkappaB activity.
A member of the tumor necrosis factor (TNF) receptor-associated factor (TRAF) family was identified in Drosophila. DTRAF1 contains 7 zinc finger domains followed by a TRAF domain, similar to mammalian TRAFs and other members of the family identified in data bases from Caenorhabditis elegans, Arabidopsis, and Dictyostelium. Analysis of DTRAF1 binding to different members of the human TNF receptor family showed that this protein can interact through its TRAF domain with the p75 neurotrophin receptor and weakly with the lymphotoxin-beta receptor. DTRAF1 can also self-associate and binds to human TRAF1, 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 induce significant NFkappaB activation when overexpressed in mammalian cells, although it specifically increased NFkappaB induction by TRAF6. In contrast, TRAF2-mediated NFkappaB induction was partially inhibited by DTRAF1. Mutants of DTRAF1 lacking the N-terminal region inhibited NFkappaB induction by either TRAF2 or TRAF6. DTRAF1 specifically associated with the regulatory N-terminal domain of Pelle, a Drosophila homolog of the human kinase interleukin-1 receptor-associated kinase (IRAK). Interestingly, though Pelle and DTRAF1 individually were unable to induce NFkappaB in a human cell line, co-expression of Pelle and DTRAF1 resulted in significant NFkappaB activity. Interactions of DTRAF1 with human TRAF-, TNF receptor-, and IAP-family proteins imply strong evolutionary conservation of TRAF protein structure and function throughout Metazoan evolution.
Zapata
J M
JM
The Burnham Institute, La Jolla, California 92037, USA.
Matsuzawa
S
S
Godzik
A
A
Leo
E
E
Wasserman
S A
SA
Reed
J C
JC
D000595:Amino Acid Sequence; D000818:Animals; D017360:Arabidopsis; D017173:Caenorhabditis elegans; D004023:Dictyostelium; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D047990:TNF Receptor-Associated Factor 1; D047992:TNF Receptor-Associated Factor 2; D053449:TNF Receptor-Associated Factor 4; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D016335:Zinc Fingers
D029721:Drosophila Proteins; D016328:NF-kappa B; D011506:Proteins; D017472:Receptors, Interleukin-1; D047990:TNF Receptor-Associated Factor 1; D047992:TNF Receptor-Associated Factor 2; D053449:TNF Receptor-Associated Factor 4; C506367:TRAF4 protein, human; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D011494:Protein Kinases; C079896:pll protein, Drosophila; D053592:Interleukin-1 Receptor-Associated Kinases; D017346:Protein Serine-Threonine Kinases