Stimulator of interferon genes (STING) is an endoplasmic-reticulum resident protein, playing essential roles in immune responses against microbial infections. However, over-activation of STING is accompanied by excessive inflammation and results in various diseases, including autoinflammatory diseases and cancers. Therefore, precise regulation of STING activities is critical for adequate immune protection while limiting abnormal tissue damage. Numerous mechanisms regulate STING to maintain homeostasis, including protein-protein interaction and molecular modification. Among these, post-translational modifications (PTMs) are key to accurately orchestrating the activation and degradation of STING by temporarily changing the structure of STING. In this review, we focus on the emerging roles of PTMs that regulate activation and inhibition of STING, and provide insights into the roles of the PTMs of STING in disease pathogenesis and as potential targeted therapy.
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http://dx.doi.org/10.3389/fimmu.2022.888147 | DOI Listing |
Sci China Life Sci
January 2025
The Key Laboratory of Medical Molecular Cell Biology of Shanxi Province, Institutes of Biomedical Sciences, Shanxi University, Taiyuan, 030006, China.
The cGAS-STING pathway plays a crucial role in the innate immune system by detecting mislocalized double-stranded DNA (dsDNA) in the cytoplasm and triggering downstream signal transduction. Understanding the mechanisms by which cGAS and STING operate is vital for gaining insights into the biology of this pathway. This review provides a detailed examination of the structural features of cGAS and STING proteins, with a particular emphasis on their activation and inhibition mechanisms.
View Article and Find Full Text PDFDermatol Ther (Heidelb)
January 2025
Medical Direction Pharmaceutical Care and Medical Dermatology, Pierre Fabre Dermatologie, Les Cauquillous, 81500, Lavaur, France.
Introduction: Topical 5-fluorouracil (5-FU), 5% or 4% cream, is recommended among first-line treatments for actinic keratosis (AK). Local skin reactions (LSRs) are an expected and transient response to treatment with 5-FU but can lead to treatment discontinuation when severe. This analysis aimed to investigate whether the severity of LSRs during the treatment was associated with lesion clearance assessed 4 weeks after completing treatment.
View Article and Find Full Text PDFCurr Pharm Des
January 2025
School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, China.
cGAS (cyclic GMP-AMP synthase)-STING (stimulator of interferon genes) pathway is an natural immune response signaling pathway in the human body that is essential for sensing abnormal DNA aggregation in the cell. When the cGAS protein senses abnormal or damaged DNA, it forms a second messenger called cyclic dinucleotide (cGAMP). The cycled dinucleotide will activate the downstream STING protein, thereby inducing the expression of inflammatory cytokines such as type I interferon, which binds to receptors on its own cell membrane and ultimately initiates multiple immune response pathways.
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