{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["de Oliveira Mann CC"],"funding":["Eugene V. Weissman","Searle Scholars Program","Howard Hughes Medical Institute","NCRR NIH HHS","NIAID NIH HHS","NIH","Pew Biomedical Scholars Program","Cancer Research Institute","Sloan Research Fellowship","V Foundation","NIDDK NIH HHS","Burroughs Wellcome Fund","Charles H. Hood Foundation","DFCI-Novartis Drug Discovery Program","Claudia Adams Barr Program for Innovative Cancer Research","NIH-ORIP HEI","NIGMS NIH HHS","NIGMS"],"pagination":["1165-1175.e5"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7733315"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["27(4)"],"pubmed_abstract":["Stimulator of interferon genes (STING) is a key regulator of type I interferon and pro-inflammatory responses during infection, cellular stress, and cancer. Here, we reveal a mechanism for how STING balances activation of IRF3- and NF-κB-dependent transcription and discover that acquisition of discrete signaling modules in the vertebrate STING C-terminal tail (CTT) shapes downstream immunity. As a defining example, we identify a motif appended to the CTT of zebrafish STING that inverts the typical vertebrate signaling response and results in dramatic NF-κB activation and weak IRF3-interferon signaling. We determine a co-crystal structure that explains how this CTT sequence recruits TRAF6 as a new binding partner and demonstrate that the minimal motif is sufficient to reprogram human STING and immune activation in macrophage cells. Together, our results define the STING CTT as a linear signaling hub that can acquire modular motifs to readily adapt downstream immunity."],"journal":["Cell reports"],"pubmed_title":["Modular Architecture of the STING C-Terminal Tail Allows Interferon and NF-κB Signaling Adaptation."],"pmcid":["PMC7733315"],"funding_grant_id":["AI093589","K99AI30258","T32 AI007512","R01 AI116550","U19 AI133524","K99 AI130258","AI133524","T32AI007512","P30 DK034854","P30DK34854","S10 RR029205","P41 GM103403","R01 AI093589","AI116550"],"pubmed_authors":["Orzalli MH","Lee ASY","de Oliveira Mann CC","King DS","Kranzusch PJ","Kagan JC"],"additional_accession":[]},"is_claimable":false,"name":"Modular Architecture of the STING C-Terminal Tail Allows Interferon and NF-κB Signaling Adaptation.","description":"Stimulator of interferon genes (STING) is a key regulator of type I interferon and pro-inflammatory responses during infection, cellular stress, and cancer. Here, we reveal a mechanism for how STING balances activation of IRF3- and NF-κB-dependent transcription and discover that acquisition of discrete signaling modules in the vertebrate STING C-terminal tail (CTT) shapes downstream immunity. As a defining example, we identify a motif appended to the CTT of zebrafish STING that inverts the typical vertebrate signaling response and results in dramatic NF-κB activation and weak IRF3-interferon signaling. We determine a co-crystal structure that explains how this CTT sequence recruits TRAF6 as a new binding partner and demonstrate that the minimal motif is sufficient to reprogram human STING and immune activation in macrophage cells. Together, our results define the STING CTT as a linear signaling hub that can acquire modular motifs to readily adapt downstream immunity.","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Apr","modification":"2024-10-19T12:54:43.764Z","creation":"2021-02-20T14:29:07Z"},"accession":"S-EPMC7733315","cross_references":{"pubmed":["31018131"],"doi":["10.1016/j.celrep.2019.03.098"]}}