STING palmitoylation as a therapeutic target

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisReviewForskningpeer review

DOI

  • Anne Louise Hansen
  • Kojiro Mukai, Laboratory of Organelle Pathophysiology, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, 980-8578, Miyagi, Japan.
  • ,
  • Francisco J Schopfer, Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
  • ,
  • Tomohiko Taguchi, Laboratory of Organelle Pathophysiology, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, 980-8578, Miyagi, Japan. tomohiko.taguchi.b8@tohoku.ac.jp.
  • ,
  • Christian K Holm

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-Goutieres 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.

OriginalsprogEngelsk
TidsskriftCellular & molecular immunology
Vol/bind16
Nummer3
Sider (fra-til)236-241
Antal sider6
ISSN1672-7681
DOI
StatusUdgivet - mar. 2019

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