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

ABSTRACT: Pathogen-associated molecular pattern (PAMP) recognition leads to TANK-binding kinase (TBK1) polyubiquitination and activation by transautophosphorylation, resulting in IFN-? production. Here, we describe a mouse model of optineurin insufficiency (Optn?(157) ) in which the TBK1-interacting N-terminus of optineurin was deleted. PAMP-stimulated cells from Optn?(157) mice had reduced TBK1 activity, no phosphorylation of optineurin Ser(187) , and mounted low IFN-? 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.

SUBMITTER: Meena NP

PROVIDER: S-EPMC4879041 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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

Meena Netra Pal NP Zhu Guozhi G Mittelstadt Paul R PR Giardino Torchia Maria Letizia ML Pourcelot Marie M Arnoult Damien D Ashwell Jonathan D JD Munitic Ivana I

FEBS letters 20160504 10

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 ...[more]

PMID: 27086836

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