Delineating the Interaction Between TRAF1 and the Linear-Ubiquitin Chain Assembly Complex
Dhillon, Bipandeep Singh
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Tumour necrosis factor receptor (TNFR)-associated factor 1 (TRAF1) is a signaling adaptor that plays opposing roles in NF-B activation downstream of TNFR and Toll-like receptor (TLR) family members. Furthermore, TRAF1 has been associated with an increased risk of RA, however, the exact mechanisms regarding its role in RA are still unclear. Therefore, isolating its opposing effects on NF-B activation would provide an excellent model to study the exact role of TRAF1 in-vivo and in disease states such as RA and other inflammatory diseases, where multiple signaling pathways are involved. Since downstream of TLRs, TRAF1 negatively regulates NF-B by sequestering the Linear-Ubiquitin Chain Assembly Complex (LUBAC), we developed various TRAF1 truncations and mutants and by utilizing co-immunoprecipitation determined the exact protein-to-protein interaction between TRAF1 and LUBAC components. This will help create a TRAF1 mutant that does not associate with LUBAC, while maintaining its role in TNFR and other signaling pathways.