Modulation of the Interferon Antiviral Response by the TBK1/IKKi Adaptor Protein TANK

• Published in: The Journal of biological chemistry Vol. 282; no. 16; pp. 11817 - 11826
• Main Authors: Guo, Beichu, Cheng, Genhong
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.04.2007; American Society for Biochemistry and Molecular Biology
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Adaptor Proteins, Signal Transducing - physiology; Animals; Antiviral Agents - pharmacology; Cell Line; Dose-Response Relationship, Drug; Fibroblasts - metabolism; Humans; I-kappa B Kinase - metabolism; Interferons - metabolism; Mice; Models, Biological; Protein Binding; Protein Structure, Tertiary; Protein-Serine-Threonine Kinases - metabolism; Signal Transduction
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M700017200

Induction of type I interferons can be triggered by viral components through Toll-like receptors or intracellular viral receptors such as retinoic acid-inducible gene I. Here, we demonstrate that the TRAF (tumor necrosis factor receptor-associated factor) family member-associated NF-κB activator (TANK) plays an important role in interferon induction through both retinoic acid-inducible gene I- and Toll-like receptor-dependent pathways. TANK forms complexes with both upstream signal mediators, such as Cardif/MAVS/IPS-1/VISA, TRIF (Toll-interleukin-1 receptor domain-containing adaptor inducing interferon-β), and TRAF3 and downstream mediators TANK-binding kinase 1, inducible IκB kinase, and interferon regulatory factor 3. In addition, it synergizes with these signaling components in interferon induction. Specific knockdown of TANK results in reduced type I interferon production, increased viral titers, and enhanced cell sensitivity to viral infection. Thus, TANK may be a critical adaptor that regulates the assembly of the TANK-binding kinase 1-inducible IκB kinase complex with upstream signaling molecules in multiple antiviral pathways.