@article{0a914b2bcc4c4f569872e357572b195d,
title = "STING palmitoylation as a therapeutic target",
abstract = "Gain-of-function mutations in the STING-encoding gene TMEM173 are central to the pathology of the autoinflammatory disorder STING-associated vasculopathy with onset in infancy (SAVI). Furthermore, excessive activity of the STING signaling pathway is associated with autoinflammatory diseases, including systemic lupus erythematosus and Aicardi–Gouti{\`e}res syndrome (AGS). Two independent studies recently identified pharmacological inhibitors of STING. Strikingly, both types of compounds are reactive nitro-containing electrophiles that target STING palmitoylation, a posttranslational modification necessary for STING signaling. As a consequence, the activation of downstream signaling molecules and the induction of type I interferons were inhibited. The compounds were effective at ameliorating inflammation in a mouse model of AGS and in blocking the production of type I interferons in primary fibroblasts from SAVI patients. This mini-review focuses on the roles of palmitoylation in STING activation and signaling and as a pharmaceutical target for drug development.",
keywords = "Inflammation, Interferonopathies, Palmitoylation, SAVI, STING",
author = "Hansen, {Anne Louise} and Kojiro Mukai and Schopfer, {Francisco J.} and Tomohiko Taguchi and Holm, {Christian K.}",
note = "Funding Information: This research was supported by the following funders. A.L.H was supported by C.C. Klestrup og Hustru Henriette Klestrup{\textquoteright}s Mindefond, Direkt{\o}r Jacob Madsen og Hustru Olga Madsen{\textquoteright}s Fond, Den B{\o}hmske Fond, Lily Benthine Lunds Fond af 1.6.1978 in addition to a PhD fellowship from the Graduate School of Health at Aarhus University. K.M. was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant JP17K15445, ONO Medical Research Foundation, Takeda Science Foundation, and the Mochida Memorial Foundation for Medical and Pharmaceutical Research. F.J.S. was supported by NIH grants R01-GM125944 and R01-DK112854 and the American Heart Association AHA17GRN33660955. T.T. was supported by JSPS KAKENHI Grants JP16H04782 and JP15H05903 and AMED-PRIME. C.H.K. was supported by H{\o}rslevsfonden, Agnes and Poul Friis Fond, Brdr. Hartmanns Fond, Oda og Hans Svenningsens Fond, Augustinus Fonden, and Hede Nielsens Fond. Publisher Copyright: {\textcopyright} 2019, The Author(s).",
year = "2019",
month = mar,
day = "1",
doi = "10.1038/s41423-019-0205-5",
language = "English",
volume = "16",
pages = "236--241",
journal = "Cellular and Molecular Immunology",
issn = "1672-7681",
publisher = "Nature Publishing Group",
number = "3",
}