Implications of tissue specific STING protein flux and abundance on inflammation and the development of targeted therapeutics Article Swipe
Thomas E. Angel
,
Zhuo Chen
,
Ahmed Moghieb
,
Sze‐Ling Ng
,
Allison M. Beal
,
Carol A. Capriotti
,
Leonard Azzarano
,
Debra Comroe
,
Michael Adam
,
Patrick Moore
,
Bao Hoang
,
Kelly Blough
,
Joanne Kuziw
,
Joshi M. Ramanjulu
,
G. Scott Pesiridis
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1371/journal.pone.0319216
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1371/journal.pone.0319216
Drugs targeting the ER-resident innate immune receptor Stimulator of Interferon Genes (STING) are in development for treatments of cancer and inflammatory diseases. Accurate determination of STING receptor levels in normal and disease tissue is an essential component of modeling pharmacology and drug-target disposition. Using metabolic labeling with deuterium oxide paired with high resolution mass spectrometry, we report the protein fractional synthesis rates and turnover of STING in wild-type (C57BL/6) and inflamed mice carrying the Trex1 D18N mutation (Trex1 D18N ) as a STING-dependent model of human Acardi-Goutiéres syndrome. Remarkably, STING protein half-life is tissue specific with the shortest half-life of 4 days in colon and lymph node and longest half-life of 24 days in skeletal muscle. Despite the relative increase in STING protein abundance in the inflamed Trex1 D18N mouse, the overall kinetics of protein degradation and resynthesis was similar between Trex1 D18N and WT mice. The extent of tissue specific interferon stimulated gene transcription, a hallmark of SLE linked pathophysiology, correlates with the extend of increased STING levels in Trex1 D18N tissues and appears inversely proportional to the turnover rate of STING. Understanding STING’s fractional protein synthesis rate and half-life provides a valuable component of quantitative modeling of drug pharmacology, dose frequency and targeting tissues of STING directed therapies.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1371/journal.pone.0319216
- https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0319216&type=printable
- OA Status
- gold
- References
- 72
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4407938146
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4407938146Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1371/journal.pone.0319216Digital Object Identifier
- Title
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Implications of tissue specific STING protein flux and abundance on inflammation and the development of targeted therapeuticsWork title
- Type
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articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-02-25Full publication date if available
- Authors
-
Thomas E. Angel, Zhuo Chen, Ahmed Moghieb, Sze‐Ling Ng, Allison M. Beal, Carol A. Capriotti, Leonard Azzarano, Debra Comroe, Michael Adam, Patrick Moore, Bao Hoang, Kelly Blough, Joanne Kuziw, Joshi M. Ramanjulu, G. Scott PesiridisList of authors in order
- Landing page
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https://doi.org/10.1371/journal.pone.0319216Publisher landing page
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https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0319216&type=printableDirect link to full text PDF
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
- OA URL
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https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0319216&type=printableDirect OA link when available
- Concepts
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Sting, Inflammation, Biology, Medicine, Pharmacology, Immunology, Aerospace engineering, EngineeringTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
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72Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| corresponding_author_ids | https://openalex.org/A5116420577, https://openalex.org/A5058044675, https://openalex.org/A5110614822, https://openalex.org/A5007328776, https://openalex.org/A5030164209, https://openalex.org/A5038365114, https://openalex.org/A5110986719, https://openalex.org/A5119128853, https://openalex.org/A5086467851, https://openalex.org/A5116420575, https://openalex.org/A5013572576, https://openalex.org/A5047360672, https://openalex.org/A5116420576, https://openalex.org/A5057693673, https://openalex.org/A5101555725 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 15 |
| corresponding_institution_ids | https://openalex.org/I1320354487, https://openalex.org/I4210114143 |
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| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.06527309 |
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