{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTANK functions as a pivotal adaptor protein in antiviral innate immune signaling, serving as a scaffold that links intracellular viral sensors and Toll‐like receptor pathways to downstream kinases such as TBK1 and IKKε. In doing so, TANK facilitates the phosphorylation of interferon regulatory factors (IRF3/7) and promotes type I interferon production, thereby contributing to efficient antiviral responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in interferon induction, TANK is integral to the regulation of NF‑κB signaling. It interacts with key mediators—including NEMO and various TRAF proteins—to assemble and modulate the IκB kinase complex in response to stimuli such as pro‐inflammatory cytokines, Toll‐like receptor ligands, and genotoxic stress. Notably, TANK is itself a target of viral proteases that cleave it at specific sites, subverting its ability to control TRAF-mediated NF‑κB activation and thereby facilitating viral evasion of host immunity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its scaffolding role in signal transduction, TANK is subject to complex post‑translational modifications—including phosphorylation, ubiquitination (both Lys63‑linked and SUMOylation) and polyubiquitination—that dynamically regulate its interactions with other proteins (for example, TRAFs, TBK1 adaptors, and E3 ligase components) and modulate the amplitude and duration of downstream immune responses. Structural analyses have delineated specific binding motifs involved in TRAF recognition, while genetic studies have linked polymorphisms in the TANK gene to varied outcomes in inflammatory diseases, antiviral responses, neoplastic conditions, and even behavioral traits such as alcohol consumption. Moreover, TANK’s partnerships with mitochondrial regulators and other adaptors extend its influence to processes ranging from keratinocyte immune responses and placental development to bone metabolism and neuro-oncology."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "25"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Beichu Guo, Genhong Cheng "}, {"type": "b", "children": [{"type": "t", "text": "Modulation of the interferon antiviral response by the TBK1/IKKi adaptor protein TANK."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M700017200"}], "href": "https://doi.org/10.1074/jbc.M700017200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17327220"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17327220"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Grigory Ryzhakov, Felix Randow "}, {"type": "b", "children": [{"type": "t", "text": "SINTBAD, a novel component of innate antiviral immunity, shares a TBK1-binding domain with NAP1 and TANK."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.emboj.7601743"}], "href": "https://doi.org/10.1038/sj.emboj.7601743"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17568778"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17568778"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jean-Stéphane Gatot, Romain Gioia, Tieu-Lan Chau, et al. 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