Negative-feedback regulation is a broad and pivotal biological event to maintain the homeostasis of the host. Viral DNA species derived from DNA viruses can activate STING signaling to produce pro-inflammatory cytokines and type I interferon, which further recruit immune cells or induce interferon stimulated genes (ISGs) to clear viral infection. However, excessive STING-signaling activation has been shown to induce autoimmune disease. Thus, it is important to turn off STING signaling when it has been activated. Researchers from Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences (SIBS) of Chinese Academy of Sciences revealed the novel function of TRIM30α in negatively regulating intracellular DNA and DNA virus-triggered response by targeting STING.
Under the supervision of Prof. SUN Bing, WANG Yanming, LIAN Qiaoshi and their colleagues identified E3 ubiquitin ligase TRIM30α was induced by herpes simplex virus type 1 (HSV-1) infection in dendritic cells (DCs). Knockdown or genetic ablation of TRIM30α augmented the type I IFNs and interleukin-6 response to intracellular DNA and DNA viruses. Trim30α-deficient mice were more resistant to DNA virus infection. Biochemical analyses showed that TRIM30α interacted with STING and promoted the degradation of STING via K48-linked ubiquitination at Lys275 through a proteasome-dependent pathway. These findings indicate that TRIM30α is a negative-feedback regulator of STING pathway, which helps the host to avoid excessive response and maintain homeostasis.
This study entitled “TRIM30α is a Negative-Feedback Regulator of the Intracellular DNA and DNA Virus-Triggered Response by Targeting STING” was published online in PLoS Pathogens in June 26, 2015.
This work was supported by the Ministry of Science and Technology of China and the National Natural Science Foundation of China.
CONTACT:
SUN Bing, Principal Investigator
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
Shanghai 200031, China.
E-mail: bsun@sibs.ac.cn
Phone: +86-21-54921375
Fig. TRIM30α expression was induced upon cytosolic DNA stimulation. Then TRIM30α promotes the degradation of STING via K48-linked ubiquitination through a proteasome-dependent pathway.
(Image provided by Prof. SUN Bing`s group)
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