STING palmitoylation as a therapeutic target

Anne Louise Hansen, Kojiro Mukai, Francisco J. Schopfer, Tomohiko Taguchi, Christian K. Holm

研究成果: Review article査読

19 被引用数 (Scopus)

抄録

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 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.

本文言語English
ページ(範囲)236-241
ページ数6
ジャーナルCellular and Molecular Immunology
16
3
DOI
出版ステータスPublished - 2019 3 1

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学
  • 感染症

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