Ying Qin, Min Wang, Xintong Meng, Mengge Wang, Haojia Jiang, Yanjie Gao, Jingxin Li, Chunyuan Zhao, Chaofeng Han, Wei Zhao, Xuexing Zheng
Optimal activation of stimulator of interferon genes (STING) protein is crucial for host defenses against pathogens and avoiding detrimental effects. Various post-translational modifications control STING activity. However, the function of interferon (IFN)-stimulated gene (ISG) 15 modification (ISGylation) in controlling STING stability and activation is unclear. Here, we show that the E3 ISGylation ligases HECT domain- and RCC1-like domain-containing proteins (HERCs; HERC5 in humans and HERC6 in mice) facilitate STING activation by mediating ISGylation of STING at K150, preventing its K48-linked ubiquitination and degradation...
April 21, 2024: Cell Reports