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TRIM69 potentiates the cGAS-STING signalling pathway by promoting STING ubiquitination
Shixin Chen1, Li Yi2, Mengzhou Xue3
1College of Medicine, Lishui University, Lishui 323000, China.
Cellular Signalling
|March 22, 2026
Summary
The E3 ubiquitin ligase TRIM69 enhances antiviral immunity by activating the cGAS-STING pathway. TRIM69 directly ubiquitinates STING, promoting its dimerization and downstream signaling for type I interferon production.
Area of Science:
- Immunology
- Molecular Biology
- Cellular Signaling
Background:
- The cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) pathway detects cytosolic DNA.
- Activation of the stimulator of interferon genes (STING) by cGAMP initiates type I interferon (IFN-I) production, crucial for antiviral innate immunity.
Purpose of the Study:
- To investigate the role of the E3 ubiquitin ligase TRIM69 in the cGAS-STING pathway.
- To elucidate the mechanism by which TRIM69 regulates IFN-I production during antiviral responses.
Main Methods:
- Co-immunoprecipitation assays to demonstrate direct interaction between TRIM69 and STING.
- Western blotting to detect ubiquitination of STING and activation of downstream kinases.
- Analysis of IFN-I production in response to DNA sensing.
Main Results:
- TRIM69 directly binds to STING.
- TRIM69 mediates K63-linked ubiquitination of STING, enhancing its dimerization.
- This ubiquitination leads to increased activation of TBK1 and subsequent IFN-I production.
Conclusions:
- TRIM69 is a novel positive regulator of the cGAS-STING cytosolic DNA-sensing pathway.
- TRIM69-induced STING ubiquitination is essential for effective antiviral innate immunity.
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