E-GEOD-51199 - Cyclic-Di-Nucleotides Trigger ULK1 (ATG1) Phosphorylation of STING to Prevent Sustained Innate Immune Signaling

Released on 10 October 2013, last updated on 3 June 2014
Mus musculus
Samples (6)
Array (1)
Protocols (7)
Activation of the STING (Stimulator of Interferon Genes) pathway by microbial or self-DNA, as well as cyclic di nucleotides (CDN), results in the induction of numerous genes that suppress pathogen replication and facilitate adaptive immunity. However, sustained gene transcription is rigidly prevented to avoid lethal STING-dependent pro-inflammatory disease by mechanisms that remain unknown. We demonstrate here that after autophagy-dependent STING delivery of TBK1 (TANK-binding kinase 1) to endosomal/lysosomal compartments and activation of transcription factors IRF3 (interferon regulatory factors 3) and NF-κB (nuclear factor kappa beta), that STING is subsequently phosphorylated by serine/threonine UNC-51-like kinase (ULK1/ATG1) and IRF3 function is suppressed. ULK1 activation occurred following disassociation from its repressor adenine monophosphate activated protein kinase (AMPK), and was elicited by CDN’S generated by the cGAMP synthase, cGAS. Thus, while CDN’s may initially facilitate STING function, they subsequently trigger negative-feedback control of STING activity, thus preventing the persistent transcription of innate immune genes. Total RNA obtained from primary STING deficient mouse embryonic fibroblast reconstituted with mSTING (W), S365A variant (A), or S365D variant (D). These cells were transfected with dsDNA (ISD) for 3 hours.
Experiment type
transcription profiling by array 
BIJU ISSAC <bissac@med.miami.edu>, Glen N Barber, Hiroyasu Konno, Keiko Konno
Investigation descriptionE-GEOD-51199.idf.txt
Sample and data relationshipE-GEOD-51199.sdrf.txt
Processed data (1)E-GEOD-51199.processed.1.zip
Additional data (1)E-GEOD-51199.additional.1.zip
Array designA-MEXP-1175.adf.txt