Human STING Is Regulated by an Autoinhibitory Mechanism for Type I Interferon Production

Autor: Shishi Qi, Changwan Wang, Rui Zhang, Junyan Zhu, Xianteng Hou, Yingbo Jiang, Jiaxin Li, Miao Ren, Muwang Li, Fajian Hou
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Journal of Innate Immunity, Pp 1-14 (2022)
Druh dokumentu: article
ISSN: 1662-811X
1662-8128
DOI: 10.1159/000521734
Popis: Stimulator of interferon genes (STING) plays a pivotal role in type I interferon-mediated innate immune response to the cytoplasmic detection of aberrant DNA. STING is a membrane protein localized in endoplasmic reticulum (ER), which upon stimulation translocates to Golgi apparatus and activates downstream signaling cascades. However, the mechanism regulating STING activity and significance of its intracellular traffic are not completely understood. Here we identify a novel region of human STING comprising thirteen residues within its C-terminal tail (CTT) for downstream nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) activation. We also discover that STING CTT fragment can activate downstream signaling regardless of its ER localization. In addition, we reveal that ligand-binding domain (LBD) in the middle of STING binds and confers autoinhibition to its CTT for both NF-κB- and interferon regulatory factor 3-activation. Furthermore, STING LBD can inhibit the interferon-stimulating activity of STING CTT in trans and demonstrate a dominant negative effect on endogenous STING for interferon induction. We thus uncover an important autoinhibitory mechanism modulating STING activity.
Databáze: Directory of Open Access Journals
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