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A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
Published on: January 24, 2016
The TBK1-binding domain of optineurin promotes type I interferon responses
Netra Pal Meena1, Guozhi Zhu1, Paul R Mittelstadt1
1Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
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.
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