Implications of Tissue-Specific STING Protein Flux and Abundance on Inflammation and the Development of Targeted Therapeutics

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Angel TE, et al. | 2025, February 25 | GSK‍

https://pubmed.ncbi.nlm.nih.gov/39999142/

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Research summary

This study examines the tissue-specific turnover rates and abundance of the Stimulator of Interferon Genes (STING) protein in both wild-type (WT) mice and those carrying the Trex1 D18N mutation, a model for STING-dependent inflammation. The research employs metabolic labeling with deuterium oxide and high-resolution mass spectrometry to measure STING protein synthesis rates and degradation across different tissues.

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Key outcome of the study

STING protein half-life varies significantly across tissues, ranging from 4 days in the colon and lymph nodes to 24 days in skeletal muscle. Despite increased STING abundance in Trex1 D18N mice, the protein’s degradation and resynthesis kinetics were similar to WT mice. The extent of interferon-stimulated gene transcription correlated with STING levels and was inversely proportional to its turnover rate.