title: SUMO modification of TBK1 at the adaptor-binding C-terminal coiled-coil domain contributes to its antiviral activity.
abstract: The non-canonical IKK kinase TBK1 serves as an important signal transmitter of the antiviral interferon response, but is also involved in the regulation of further processes such as autophagy. The activity of TBK1 is regulated by posttranslational modifications comprising phosphorylation and ubiquitination. This study identifies SUMOylation as a novel posttranslational TBK1 modification. TBK1 kinase activity is required to allow the attachment of SUMO1 or SUMO2/3 proteins. Since TBK1 does not bind to the E2 enzyme Ubc9, this modification most likely proceeds via trans-SUMOylation. Mass spectrometry allowed identifying K694 as the SUMO acceptor site, a residue located in the C-terminal coiled-coil domain which is exclusively responsible for the association with the adaptor proteins NAP1, Sintbad and TANK. SUMO modification at K694 contributes to the antiviral function of TBK1 and accordingly the viral protein Gam1 antagonizes this posttranslational modification.
authors.affiliation: Institute of Biochemistry, Medical Faculty, Friedrichstrasse 24, Justus-Liebig-University, 35392 Giessen, Germany.
authors.forename: Vera V
authors.initials: VV
authors.lastname: Saul
authors.affiliation: Institute for Physiological Chemistry/Biochemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Niedenthal
authors.affiliation: Hannover Medical School, Institute of Toxicology, Core Unit - Proteomics, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Pich
authors.affiliation: Institute for Virology, Philipps University Marburg, Hans-Meerwein-Strasse 2, 35043 Marburg, Germany.
authors.forename: Friedemann
authors.initials: F
authors.lastname: Weber
authors.affiliation: Institute of Biochemistry, Medical Faculty, Friedrichstrasse 24, Justus-Liebig-University, 35392 Giessen, Germany. Electronic address: lienhard.schmitz@biochemie.med.uni-giessen.de.
authors.forename: M Lienhard
authors.initials: ML
authors.lastname: Schmitz
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D058207:Sumoylation
chemical_list: D000998:Antiviral Agents; D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human
keywords: Interferon; NF-κB; Rift Valley fever (RVF) virus; SUMO; TBK1