Researchers from Shanghai Institute of Organic Chemistry found 2′3′-cGAMP can directly bind with translation elongation factor EF1A1 and lead to protein synthesis slowing down.

 

2′3′-cGAMP is generated under DNA exposed to cytosol. This phenomenon is often observed in virus infected cells and tumor cells. 2′3′-cGAMP transmits danger signal to STING and activates innate immune response to fight virus and tumors. However, other functions of 2′3′-cGAMP are less known.

 

In order to study the biological functions of 2′3′-cGAMP, it is important to know what proteins 2′3′-cGAMP can bind in mammalian cells. But, there are no tools suitable for the identification of unknown binding proteins of 2′3′-cGAMP. So researchers designed and synthesized the 2′3′-cGAMP-based photoaffinity probes that can capture and isolate 2′3′-cGAMP-binding proteins for visualization, identification and validation. Among several potential binding proteins identified from HeLa cells using these affinity probes, EF1A1 in EF1 complex, which has a pivotal role in protein synthesis, was demonstrated to associate with 2′3′-cGAMP in vitro and in cells to impede protein synthesis.

 

This study leads the researchers to think that intrinsic 2′3′-cGAMP generated in mammalian cells may also restrict virus replication and suppress tumor cell proliferation via EF1A1 as well.

 

Jiang Hong Ph.D. Professor

Tel: 021-68582396

Email: hongjiang@sioc.ac.cn