TRAF3


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TRAF3

A gene on chromosome 14q32.32 that encodes TNF receptor-associated factor 3, which regulates NF-kappaB kinase and MAP kinase activation, plays a central role in regulating B-cell survival, and is part of signalling pathways leading to cytokine and interferon production. TRAF3 is required for normal antibody isotype switching from IgM to IgG, and it plays a role in T-cell dependent immune responses as well as antiviral responses. It is an essential constituent of several E3 ubiquitin-protein ligase complexes and may promote Lys-63-linked ubiquitination of target proteins. It inhibits NF-kappaB activation in response to LTBR stimulation, as well as TRAF2-mediated NF-kappaB activation, and it downregulates proteolytic processing of NFKB2 and NF-kappaB activation. It promotes ubiquitination and proteasomal degradation of MAP3K14.
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The researchers showed that TRAF3 is not only essential for production of type I interferons, but also for production of IL-10, a protein that prevents inflammation.
The discovery that TRAF3 is also recruited to TLRs is a big step toward solving the mystery of how macrophages can pick and choose among different strategies for combating specific infections," says Hans Haecker, M.
The results of the study suggest that the specific type of immune response triggered by TLR signaling depends on the relative amounts of TRAF3 and TRAF6 that are initially recruited and the different signaling proteins each of those proteins subsequently recruit to orchestrate the immune response.