Disease relevance of Traf1

• In contrast, we find that the Drosophila TNFR-associated factor (Traf) family member Traf2 is dispensable in resistance to gram-negative bacterial infection [1].

High impact information on Traf1

• Here we show through a genetic screen that a mutant of Drosophila melanogaster tumour-necrosis factor receptor-associated factor 1 (DTRAF1) is a dominant suppressor of Reaper-induced cell death [2].
• The Mira/Pros telophase rescue seen in inscuteable mutant NBs requires DTRAF1 [3].
• This compensatory mechanism has been referred to as 'telophase rescue'. We demonstrate that the Drosophila homolog of the mammalian tumor-necrosis factor (TNF) receptor-associated factor (DTRAF1) and Eiger (Egr), the homolog of the mammalian TNF, are required for telophase rescue of Mira/Pros [3].
• DTRAF1 localizes as an apical crescent in metaphase NBs and this apical localization requires Bazooka (Baz) and Egr [3].
• Further genetic interaction analyses revealed that the apoptosis in the eye imaginal disc and the abnormal eye morphogenesis induced by DTRAF1 are dependent on JNK and its upstream kinases, Hep and DTAK1 [4].

Biological context of Traf1

• Ectopic expression of DTRAF1 in the developing eye induced apoptosis, thereby causing a rough-eye phenotype [4].
• Dynamic expression of Drosophila TRAF1 during embryogenesis and larval development [5].
• 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 [6].

Anatomical context of Traf1

• 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 [6].
• DTRAF1 is most closely related to mammalian TRAF4 which is predominantly expressed during nervous system development and in ephitelial progenitor cells [5].
• In vertebrates, TRAF proteins link these pathways also to IL-1R-related molecules and members of the TNF receptor superfamily, which orchestrate a variety of immunoregulatory processes of the innate but also of the adaptive immune system [7].

Associations of Traf1 with chemical compounds

• Our data suggest that DTRAF1 binds to Baz and acts downstream of Egr in the Mira/Pros telophase rescue pathway [3].

Regulatory relationships of Traf1

• In Drosophila, DTRAF1 is thus a good candidate for an upstream molecule that regulates the JNK pathway by interacting with, and activating, Msn [8].

Other interactions of Traf1

• Consistent with this idea, expression of a dominant-negative Msn mutant protein blocks the activation of JNK by DTRAF1 [8].
• Msn specifically binds the TRAF domain of DTRAF1 but not that of DTRAF2 [8].
• Here, we show that DTRAF1 is an in vivo regulator of c-Jun N-terminal kinase (JNK) pathway in Drosophila melanogaster [4].

References