{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSTING (stimulator of interferon genes) is a central transmembrane adaptor residing mainly in the endoplasmic reticulum that detects cytosolic nucleic acids and cyclic dinucleotides produced either directly by pathogens or indirectly through the activity of enzymes such as cGAS. Its discovery revealed that STING is indispensable for initiating innate immune signaling by activating transcription factors NF‐κB and IRF3, leading to the production of type I interferons and other antiviral cytokines. Thus, upon binding noncanonical cyclic GMP–AMP ligands generated by cGAS or directly interacting with bacterial dinucleotides, STING undergoes conformational changes that trigger a potent antiviral state and host defense against a variety of pathogens."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its core role in detecting cytosolic DNA and dinucleotide ligands, STING functions as a molecular scaffold coordinating the recruitment and activation of kinases (notably TBK1) and transcription factors. Its activity and signaling output are finely tuned by multiple post‐translational modifications—including phosphorylation, ubiquitination, and essential palmitoylation at the Golgi—as well as by interactions with diverse regulatory partners such as DDX41, IFI16, and the ER Ca²⁺ sensor STIM1. These regulatory mechanisms ensure proper STING trafficking and timely activation; moreover, several viruses (for example, dengue virus, coronaviruses, and herpesviruses) have evolved strategies to directly target STING (via proteolytic cleavage or binding interference) to evade interferon responses. In addition, feedback mechanisms such as ULK1‐mediated phosphorylation and autophagic degradation via p62/SQSTM1 serve to restrain excessive STING activity and prevent persistent proinflammatory signaling. Collectively, these molecular controls underscore STING’s role as an integration node for cellular stress, pathogen‐derived cues, and even self‐DNA released upon mitochondrial damage."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "41"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nImportantly, dysregulation or constitutive activation of STING has been implicated in a range of pathological conditions—from autoinflammatory and autoimmune disorders (including lupus and chilblain lupus) to impaired T cell proliferation and aspects of tumor biology, as well as contributing to tissue injury in infections (for example, COVID-19) and metabolic stress. Consequently, STING has emerged as a promising therapeutic target, with novel interventions ranging from directly modulating its ligand interactions (via engineered cyclic dinucleotides or metalloimmunotherapy approaches) to exploiting its regulation by cellular stress pathways for the treatment of cancer, inflammatory diseases, and age‐related dysfunction."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "42"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hiroki Ishikawa, Glen N Barber "}, {"type": "b", "children": [{"type": "t", "text": "STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature07317"}], "href": "https://doi.org/10.1038/nature07317"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18724357"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18724357"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Bo Zhong, Yan Yang, Shu Li, et al. 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