STING palmitoylation as a therapeutic target

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

Research output: Contribution to journalReview articlepeer-review

9 Citations (Scopus)

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–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.

Original languageEnglish
Pages (from-to)236-241
Number of pages6
JournalCellular and Molecular Immunology
Volume16
Issue number3
DOIs
Publication statusPublished - 2019 Mar 1

Keywords

  • Inflammation
  • Interferonopathies
  • Palmitoylation
  • SAVI
  • STING

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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