title: 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-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.
authors.affiliation: Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Netra Pal
authors.initials: NP
authors.lastname: Meena
authors.affiliation: Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Guozhi
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Mittelstadt
authors.affiliation: Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Giardino Torchia
authors.affiliation: INSERM, UMR_S 1197, Hôpital Paul Brousse, Villejuif, France.|Université Paris-Saclay, Villejuif, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Pourcelot
authors.affiliation: INSERM, UMR_S 1197, Hôpital Paul Brousse, Villejuif, France.|Université Paris-Saclay, Villejuif, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Arnoult
authors.affiliation: Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Ashwell
authors.affiliation: Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.|Laboratory of Molecular Immunology, Department of Biotechnology, University of Rijeka, Croatia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Munitic
mesh_terms: D000818:Animals; D001665:Binding Sites; D018797:Cell Cycle Proteins; D005136:Eye Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D016899:Interferon-beta / Q000378:metabolism*; D026901:Membrane Transport Proteins; D051379:Mice; D000069452:Pathogen-Associated Molecular Pattern Molecules / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017384:Sequence Deletion
chemical_list: D018797:Cell Cycle Proteins; D005136:Eye Proteins; D026901:Membrane Transport Proteins; C501288:Optn protein, mouse; D000069452:Pathogen-Associated Molecular Pattern Molecules; D016899:Interferon-beta; C498588:Tbk1 protein, mouse; D017346:Protein Serine-Threonine Kinases
keywords: TBK1; optineurin; type I interferon