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

FEBS Lett. 2016 May;590(10):1498-508. doi: 10.1002/1873-3468.12176. Epub 2016 May 4.

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 (OptnΔ(157) ) in which the TBK1-interacting N-terminus of optineurin was deleted. PAMP-stimulated cells from OptnΔ(157) mice had reduced TBK1 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 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.

Keywords: TBK1; optineurin; type I interferon.

Publication types

  • Letter

MeSH terms

  • Animals
  • Binding Sites
  • Cell Cycle Proteins
  • Eye Proteins / chemistry*
  • Eye Proteins / genetics*
  • Eye Proteins / metabolism
  • Gene Expression Regulation / drug effects
  • HEK293 Cells
  • Humans
  • Interferon-beta / metabolism*
  • Membrane Transport Proteins
  • Mice
  • Pathogen-Associated Molecular Pattern Molecules / pharmacology*
  • Phosphorylation / drug effects
  • Protein Binding
  • Protein Serine-Threonine Kinases / metabolism*
  • Sequence Deletion

Substances

  • Cell Cycle Proteins
  • Eye Proteins
  • Membrane Transport Proteins
  • Optn protein, mouse
  • Pathogen-Associated Molecular Pattern Molecules
  • Interferon-beta
  • Tbk1 protein, mouse
  • Protein Serine-Threonine Kinases