{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTumor necrosis factor receptor–associated factor 3 (TRAF3) is a highly versatile adaptor protein that plays a critical role in receptor‐mediated signal transduction. Structural and interaction studies have demonstrated that TRAF3 selectively binds to defined motifs in receptors such as BAFF‐R, CD40, LTβR, and viral proteins (e.g., EBV LMP1), thereby modulating both canonical and noncanonical NF‐κB pathways. These interactions ensure the proper balance of downstream signals that are essential for B cell homeostasis, lymphocyte activation, and the regulation of inflammatory gene expression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role as a docking protein, TRAF3 is tightly regulated by ubiquitination and deubiquitination events that control its stability and function, thereby fine‐tuning innate antiviral responses. Cellular deubiquitinating enzymes and viral deubiquitinases have been shown to remove or add specific ubiquitin chains on TRAF3, which in turn modulates the activation of NF‐κB as well as type I interferon production following RIG-I– and TLR–mediated viral sensing. Moreover, recruitment of E3 ubiquitin ligases (such as cIAP1/2) and adaptor complexes may determine whether TRAF3 promotes activation of downstream kinases or is targeted for degradation, ultimately affecting both the amplitude and quality of the antiviral and inflammatory responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond classical immune functions, emerging evidence indicates that TRAF3 also exerts critical effects in other cellular contexts. In T lymphocytes, TRAF3 is recruited into the T cell receptor–CD28 complex to optimize signaling for proper immune defense, and its deficiency impairs T cell–mediated immunity. In nonlymphoid tissues, TRAF3 has been implicated in pathological processes such as cardiac hypertrophy—where it drives hypertrophic signaling via interactions with TBK1 and downstream AKT activation—and serves as a pivotal mediator in targeted drug delivery, for example as part of a TLR4/TRAF3/mitofusin 1 complex that directs nanoparticle cargo to mitochondria. In B cells, loss-of-function mutations in TRAF3 contribute to lymphomagenesis, underscoring its tumor-suppressive properties."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "23", "end_ref": "25"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Suwan K Sinha, Sunny Zachariah, Herson I Quiñones, et al. 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