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Inducible SUMO modification of TANK alleviates its repression of TLR7 signalling
Author(s) -
Renner Florian,
Saul Vera V,
Pagenstecher Axel,
Wittwer Tobias,
Schmitz Michael Lienhard
Publication year - 2011
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2010.207
Subject(s) - psychological repression , microbiology and biotechnology , signalling , tlr7 , chemistry , biology , business , genetics , immune system , gene , gene expression , innate immune system , toll like receptor
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 ε (IKKε) and TBK1. Stimulation of TLR7 leads to inducible SUMOylation of TANK, which in turn weakens the interaction with IKKε 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.