{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["van der Horst D"],"funding":["Natur og Univers, Det Frie Forskningsråd","Novo Nordisk Fonden (Novo Nordisk Foundation)","Natur og Univers, Det Frie Forskningsråd (Natural Sciences, Danish Council for Independent Research)","European Research Council","Lundbeckfonden (Lundbeck Foundation)","Steno Diabetes Center Aarhus (SDCA)","Lundbeckfonden","Novo Nordisk Fonden"],"pagination":["283"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10920828"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["7(1)"],"pubmed_abstract":["DNA is a danger signal sensed by cGAS to engage signaling through STING to activate innate immune functions. The best-studied downstream responses to STING activation include expression of type I interferon and inflammatory genes, but STING also activates other pathways, including apoptosis. Here, we report that STING-dependent induction of apoptosis in macrophages occurs through the intrinsic mitochondrial pathway and is mediated via IRF3 but acts independently of gene transcription. By intersecting four mass spectrometry datasets, we identify SAM68 as crucial for the induction of apoptosis downstream of STING activation. SAM68 is essential for the full activation of apoptosis. Still, it is not required for STING-mediated activation of IFN expression or activation of NF-κB. Mechanistic studies reveal that protein trafficking is required and involves SAM68 recruitment to STING upon activation, with the two proteins associating at the Golgi or a post-Golgi compartment. Collectively, our work identifies SAM68 as a STING-interacting protein enabling induction of apoptosis through this DNA-activated innate immune pathway."],"journal":["Communications biology"],"pubmed_title":["SAM68 directs STING signaling to apoptosis in macrophages."],"pmcid":["PMC10920828"],"funding_grant_id":["R335-2019-2138","NNF20OC0063436","326","786602","NNF20OC0064301","NNF17OC0029042","1026-00003B","NNF18OC0030274"],"pubmed_authors":["Zhang BC","Cesari E","Sette C","Rahimic AHF","Silva da Costa L","Wu Q","van der Horst D","Jensen TI","Olagnier D","Kurmasheva N","Iversen MB","Assil S","Kollmann CF","Paludan SR","Fenton RA","Ren F","Bak RO","Marqvorsen MHS","Narita R","Mikkelsen JG","Zhao J","Schack VR"],"additional_accession":[]},"is_claimable":false,"name":"SAM68 directs STING signaling to apoptosis in macrophages.","description":"DNA is a danger signal sensed by cGAS to engage signaling through STING to activate innate immune functions. The best-studied downstream responses to STING activation include expression of type I interferon and inflammatory genes, but STING also activates other pathways, including apoptosis. Here, we report that STING-dependent induction of apoptosis in macrophages occurs through the intrinsic mitochondrial pathway and is mediated via IRF3 but acts independently of gene transcription. By intersecting four mass spectrometry datasets, we identify SAM68 as crucial for the induction of apoptosis downstream of STING activation. SAM68 is essential for the full activation of apoptosis. Still, it is not required for STING-mediated activation of IFN expression or activation of NF-κB. Mechanistic studies reveal that protein trafficking is required and involves SAM68 recruitment to STING upon activation, with the two proteins associating at the Golgi or a post-Golgi compartment. Collectively, our work identifies SAM68 as a STING-interacting protein enabling induction of apoptosis through this DNA-activated innate immune pathway.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2026-06-30T03:33:58.93Z","creation":"2026-06-30T03:30:27.234Z"},"accession":"S-EPMC10920828","cross_references":{"pubmed":["38454028"],"doi":["10.1038/s42003-024-05969-1"]}}