ULK1/2 Restricts the Formation of Inducible SINT-Speckles, Membraneless Organelles Controlling the Threshold of TBK1 Activation

Saul, Vera Vivian; Seibert, Markus; Krüger, Marcus; Jeratsch, Sylvia; Kracht, Michael; Schmitz, Michael Lienhard

TBK1 has been initially identified as a component of the antiviral response based on its ability to phosphorylate and thus activate IRF3 or IRF7 transcription factors, which in turn leads to inducible expression of type I interferons (IFN) (Fitzgerald et al., 2003; Sharma et al., 2003) . TBK1, IRF3, and further components for induced type I IFN signaling are known to translocate to perinuclear punctate structures (Saitoh et al., 2009; Seo et al., 2016) . Recent years have witnessed the identification of many additional TBK1 functions, which range from regulation of mitotic microtubule dynamics to the regulation of tumor necrosis factorinduced cell death (Lafont et al., 2018; Pillai et al., 2015; Xu et al., 2018) . Furthermore, stress-regulated TBK1 functions comprise its role in autophagy, mitophagy, and xenophagy (Heo et al., 2015; Pilli et al., 2012; Wild et al., 2011) . More recent evidence shows that TBK1 directly inhibits the AMP-activated protein kinase to increase energy storage and to repress respiration in adipose tissue, thus mediating a cross talk between immune signaling and metabolism . Basal TBK1 signaling is also required for the development of KRAS-driven cancers (Barbie et al., 2009) . Given the involvement of TBK1 in so many stress signaling pathways, TBK1 is a frequent target of viral proteins affecting its localization or protein-protein interactions (Liu et al., 2018; Onorati et al., 2016) .