TANK-binding kinase 1 (TBK1) is a non-canonical inhibitor of NF-κB kinase (IKK) that has an essential role in regulating inflammatory responses to pathogens. Following activation of toll-like receptors by viral DNA, TBK1 interacts with various partners such as STING, MAVS, and TANK to phosphorylate and activate interferon regulatory factors (IRFs) 3 and 7 as well as DEAD-box helicase 3 X-linked (DDX3X), which leads to transcriptional activation of pro-inflammatory and antiviral genes including interferon (IFN) subtypes α and β. TBK1 induces nuclear translocation of NF-κB to initiate a pro-inflammatory response via phosphorylation of NF-κB inhibitor α (NFκBIα), IKKβ, or NF-κB p65 subunit (RelA). Cytosolic localization of E. coli, Salmonella, and S. pyogenes increases in TBK1-/- murine embryonic fibroblasts, macrophages, and epithelial cells, suggesting TBK1 maintains vacuolar integrity, which is critical to bacterial clearance. TBK1 phosphorylates the autophagy receptor optineurin to enhance binding of ubiquitin-like microtubule-associated protein light chain 3 (LC3) modifiers and induce autophagic clearance of S. enterica. It also binds to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) non-structural protein 13 (Nsp13), a helicase-triphosphatase and a component of the viral replicase-transcriptase complex. Cayman’s TBK1 (human, recombinant) protein can be used for ELISA, Western blot and enzymatic assays.
