STING palmitoylation as a therapeutic target  

作　　者：Anne Louise Hansen Kojiro Mukai Francisco J.Schopfer Tomohiko Taguchi Christian K.Holm 

机构地区：[1]Department of Biomedicine,Aarhus University,8000 Aarhus C,Denmark [2]Laboratory of Organelle Pathophysiology,Department of Integrative Life Sciences,Graduate School of Life Sciences,Tohoku University,Sendai 980-8578 Miyagi,Japan [3]Department of Pharmacology and Chemical Biology,University of Pittsburgh,Pittsburgh,PA 15213,USA

出　　处：《Cellular & Molecular Immunology》2019年第3期236-241,共6页中国免疫学杂志（英文版）

摘　　要：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–Goutières syndrome(AGS).Two independent studies recently identified pharmacological inhibitors of STING.Strikingly,both types of compounds are reactive nitrocontaining 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.

关 键 词：STING PALMITOYLATION INFLAMMATION SAVI Interferonopathies 

分 类 号：R73[医药卫生—肿瘤]