RNF144A promotes antiviral responses by modulating STING ubiquitination.
Bo YangJinyong PeiChen LuYi WangMengyang ShenXiao QinYulu HuangXi YangXin ZhaoShujun MaZhishan SongYin-Ming LiangHui WangJie WangPublished in: EMBO reports (2023)
Stimulator of interferon (IFN) genes (STING, also named MITA, ERIS, MPYS, or TMEM173) plays an essential role in DNA virus- or cytosolic DNA-triggered innate immune responses. Here, we demonstrate that the RING-in-between RING (RBR) E3 ubiquitin ligase family member RING-finger protein (RNF) 144A interacts with STING and promotes its K6-linked ubiquitination at K236, thereby enhancing STING translocation from the ER to the Golgi and downstream signaling pathways. The K236R mutant of STING displays reduced activity in promoting innate immune signal transduction. Overexpression of RNF144A upregulates HSV-1- or cytosolic DNA-induced immune responses, while knockdown of RNF144A expression has the opposite effect. In addition, Rnf144a-deficient cells exhibit impaired DNA virus- or cytosolic DNA-triggered signaling, and RNF144A protects mice from DNA virus infection. In contrast, RNF144A does not affect RNA virus- or cytosolic RNA-triggered innate immune responses. Taken together, our findings identify a new positive regulator of DNA virus- or cytosolic DNA-triggered signaling pathways and a critical ubiquitination site important for fully functional STING during antiviral responses.
Keyphrases
- immune response
- circulating tumor
- cell free
- single molecule
- nucleic acid
- signaling pathway
- dendritic cells
- dna damage response
- circulating tumor cells
- cell proliferation
- poor prognosis
- metabolic syndrome
- magnetic resonance
- type diabetes
- magnetic resonance imaging
- computed tomography
- dna methylation
- gene expression
- oxidative stress
- small molecule
- epithelial mesenchymal transition
- diabetic rats
- cell death
- breast cancer cells
- protein protein
- drug induced