SAM68 directs STING signaling to apoptosis in macrophages.

Autor: van der Horst D; Department of Biomedicine, Aarhus University, Høegh Guldbergsgade 10, 8000, Aarhus C, Denmark., Kurmasheva N; Department of Biomedicine, Aarhus University, Høegh Guldbergsgade 10, 8000, Aarhus C, Denmark., Marqvorsen MHS; Department of Biomedicine, Aarhus University, Høegh Guldbergsgade 10, 8000, Aarhus C, Denmark., Assil S; Department of Biomedicine, Aarhus University, Høegh Guldbergsgade 10, 8000, Aarhus C, Denmark., Rahimic AHF; Department of Biomedicine, Aarhus University, Høegh Guldbergsgade 10, 8000, Aarhus C, Denmark., Kollmann CF; Department of Biomedicine, Aarhus University, Høegh Guldbergsgade 10, 8000, Aarhus C, Denmark., Silva da Costa L; Department of Biomedicine, Aarhus University, Høegh Guldbergsgade 10, 8000, Aarhus C, Denmark., Wu Q; Department of Biomedicine, Aarhus University, Høegh Guldbergsgade 10, 8000, Aarhus C, Denmark., Zhao J; Department of Biomedicine, Aarhus University, Høegh Guldbergsgade 10, 8000, Aarhus C, Denmark., Cesari E; GSTEP-Organoids Core Facility, IRCCS Fondazione Policlinico Agostino Gemelli, 00168, Rome, Italy., Iversen MB; Department of Biomedicine, Aarhus University, Høegh Guldbergsgade 10, 8000, Aarhus C, Denmark., Ren F; Department of Biomedicine, Aarhus University, Høegh Guldbergsgade 10, 8000, Aarhus C, Denmark., Jensen TI; Department of Biomedicine, Aarhus University, Høegh Guldbergsgade 10, 8000, Aarhus C, Denmark., Narita R; Department of Biomedicine, Aarhus University, Høegh Guldbergsgade 10, 8000, Aarhus C, Denmark., Schack VR; Department of Biomedicine, Aarhus University, Høegh Guldbergsgade 10, 8000, Aarhus C, Denmark., Zhang BC; Department of Biomedicine, Aarhus University, Høegh Guldbergsgade 10, 8000, Aarhus C, Denmark., Bak RO; Department of Biomedicine, Aarhus University, Høegh Guldbergsgade 10, 8000, Aarhus C, Denmark., Sette C; GSTEP-Organoids Core Facility, IRCCS Fondazione Policlinico Agostino Gemelli, 00168, Rome, Italy.; Department of Neuroscience, Section of Human Anatomy, Catholic University of the Sacred Hearth, 00168, Rome, Italy., Fenton RA; Department of Biomedicine, Aarhus University, Høegh Guldbergsgade 10, 8000, Aarhus C, Denmark., Mikkelsen JG; Department of Biomedicine, Aarhus University, Høegh Guldbergsgade 10, 8000, Aarhus C, Denmark., Paludan SR; Department of Biomedicine, Aarhus University, Høegh Guldbergsgade 10, 8000, Aarhus C, Denmark. srp@biomed.au.dk., Olagnier D; Department of Biomedicine, Aarhus University, Høegh Guldbergsgade 10, 8000, Aarhus C, Denmark. olagnier@biomed.au.dk.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2024 Mar 07; Vol. 7 (1), pp. 283. Date of Electronic Publication: 2024 Mar 07.
DOI: 10.1038/s42003-024-05969-1
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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