The TBK 1‐binding domain of optineurin promotes type I interferon responses

Pathogen‐associated molecular pattern ( PAMP ) recognition leads to TANK ‐binding kinase ( TBK 1) polyubiquitination and activation by transautophosphorylation, resulting in IFN ‐β production. Here, we describe a mouse model of optineurin insufficiency (OptnΔ 157 ) in which the TBK 1‐interacting N‐terminus of optineurin was deleted. PAMP ‐stimulated cells from OptnΔ 157 mice had reduced TBK 1 activity, no phosphorylation of optineurin Ser 187 , and mounted low IFN ‐β responses. In contrast to pull‐down assays where the presence of N‐terminus was sufficient for TBK 1 binding, both the N‐terminal and the ubiquitin‐binding regions of optineurin were needed for PAMP ‐induced binding. This report establishes optineurin as a positive regulator TBK 1 via a bipartite interaction between these molecules.