# Regulation of the STING pathway under sterile conditions

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $390,000

## Abstract

PROJECT SUMMARY
The type I interferons (IFN) play a pivotal role in antiviral immune responses. As aberrant immune responses
can be harmful to the host, innate immune signaling pathways are tightly regulated to minimize tissue damage.
Aberrant activation of type I IFNs often leads to onset of inflammatory diseases including systemic lupus
erythematosus (SLE), Aicardi-Goutieres syndrome (AGS) and vasculopathy. Despite a tremendous interest in
uncovering the mechanisms underlying activation of the type I IFN signaling pathway, there is negligible
understanding of mechanisms maintaining the resting state of this pathway. The endoplasmic reticulum (ER) is
a major cellular organelle for protein synthesis and Ca2+ storage, that also acts as a signaling hub for the type I
IFN responses. A major signaling adaptor for the type I IFN response, STING (stimulator of interferon genes,
TMEM173) is located at the ER and, after sensing cytosolic DNA, translocates to the ER-Golgi intermediate
compartment (ERGIC) and the Golgi with the protein kinase TANK-binding kinase 1 (TBK1) to activate the
transcription factor, interferon regulatory factor 3 (IRF3). The rate liming step for activation of the STING pathway
is exit of STING from the ER. It was suggested that “ER retention factors” should exist to prevent aberrant
activation of STING, but the molecular identity of these factors is currently not known. This study stems from
identification of STIM1 as an interacting partner of STING. Accordingly, in this proposal we will uncover the
molecular mechanisms involved in STIM1-mediated regulation of the STING pathway as well as physiological
role of STIM1 in activation of the STING pathway after induction of autoimmunity. A mechanistic understanding
of how the inactive state of type I IFN response is maintained can have therapeutic potential to alleviate chronic
inflammatory diseases, and in a long term, enhance vaccination efficacy and checkpoint blockade-based cancer
therapy.

## Key facts

- **NIH application ID:** 10051153
- **Project number:** 1R01AI146352-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Sonal Srikanth
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $390,000
- **Award type:** 1
- **Project period:** 2020-08-13 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10051153

## Citation

> US National Institutes of Health, RePORTER application 10051153, Regulation of the STING pathway under sterile conditions (1R01AI146352-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10051153. Licensed CC0.

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