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

First Author  Meena NP Year  2016
Journal  FEBS Lett Volume  590
Issue  10 Pages  1498-508
PubMed ID  27086836 Mgi Jnum  J:233694
Mgi Id  MGI:5787866 Doi  10.1002/1873-3468.12176
Citation  Meena NP, et al. (2016) The TBK1-binding domain of optineurin promotes type I interferon responses. FEBS Lett 590(10):1498-508
abstractText  Pathogen-associated molecular pattern (PAMP) recognition leads to TANK-binding kinase (TBK1) polyubiquitination and activation by transautophosphorylation, resulting in IFN-beta production. Here, we describe a mouse model of optineurin insufficiency (OptnDelta(157) ) in which the TBK1-interacting N-terminus of optineurin was deleted. PAMP-stimulated cells from OptnDelta(157) mice had reduced TBK1 activity, no phosphorylation of optineurin Ser(187) , and mounted low IFN-beta 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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