title: Inducible SUMO modification of TANK alleviates its repression of TLR7 signalling.
abstract: Adaptor proteins allow temporal and spatial coordination of signalling. In this study, we show SUMOylation of the adaptor protein TANK and its interacting kinase TANK-binding kinase 1 (TBK1). Modification of TANK by the small ubiquitin-related modifier (SUMO) at the evolutionarily conserved Lys 282 is triggered by the kinase activities of IκB kinase ɛ (IKKɛ) and TBK1. Stimulation of TLR7 leads to inducible SUMOylation of TANK, which in turn weakens the interaction with IKKɛ and thus relieves the negative function of TANK on signal propagation. Reconstitution experiments show that an absence of TANK SUMOylation impairs inducible expression of distinct TLR7-dependent target genes, providing a molecular mechanism that allows the control of TANK function.
authors.affiliation: Institute of Biochemistry, Medical Faculty, Justus-Liebig-University, Friedrichstrasse 24, Giessen 35392, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Renner
authors.forename: Vera V
authors.initials: VV
authors.lastname: Saul
authors.forename: Axel
authors.initials: A
authors.lastname: Pagenstecher
authors.forename: Tobias
authors.initials: T
authors.lastname: Wittwer
authors.forename: Michael Lienhard
authors.initials: ML
authors.lastname: Schmitz
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D003546:Cysteine Endopeptidases; D010450:Endopeptidases / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D010766:Phosphorylation; D000075223:Poly-ADP-Ribose Binding Proteins; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D025842:SUMO-1 Protein / Q000378:metabolism*; D015398:Signal Transduction; D051199:Toll-Like Receptor 7 / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C491731:IKBKG protein, human; C485891:PIAS4 protein, human; D000075223:Poly-ADP-Ribose Binding Proteins; D050828:Protein Inhibitors of Activated STAT; D011993:Recombinant Fusion Proteins; D025842:SUMO-1 Protein; C484406:TANK protein, human; C495348:TLR7 protein, human; D051199:Toll-Like Receptor 7; D051550:I-kappa B Kinase; D010450:Endopeptidases; C404512:SENP1 protein, human; D003546:Cysteine Endopeptidases