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The TBK 1‐binding domain of optineurin promotes type I interferon responses
Author(s) -
Meeetra Pal,
Zhu Guozhi,
Mittelstadt Paul R.,
Giardino Torchia Maria Letizia,
Pourcelot Marie,
Arnoult Damien,
Ashwell Jonathan D.,
Munitic Ivana
Publication year - 2016
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12176
Subject(s) - optineurin , phosphorylation , microbiology and biotechnology , chemistry , ubiquitin , plasma protein binding , biology , biochemistry , mutation , gene
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.