The TBK1‐binding domain of optineurin promotes type I interferon responses

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Abstract
Pathogen‐associated molecular pattern (PAMP) recognition leads to TANK‐binding kinase (TBK1) polyubiquitination and activation by transautophosphorylation, resulting in IFN‐β production. Here, we describe a mouse model of optineurin insufficiency (OptnΔ157) in which the TBK1‐interacting N‐terminus of optineurin was deleted. PAMP‐stimulated cells from OptnΔ157 mice had reduced TBK1 activity, no phosphorylation of optineurin Ser187, and mounted low IFN‐β responses. In contrast to pull‐down assays where the presence of N‐terminus was sufficient for TBK1 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 TBK1 via a bipartite interaction between these molecules.
Funding Information
  • National Cancer Institute
  • National Institutes of Health
  • Hrvatska Zaklada za Znanost (#7459)
  • Agence Nationale de Recherches sur le Sida et les Hépatites Virales

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