ERIS, an endoplasmic reticulum IFN stimulator, activates innate immune signaling through dimerization

We report here the identification and characterization of a protein, ERIS, an endoplasmic reticulum (ER) IFN stimulator, which is a strong type I IFN stimulator and plays a pivotal role in response to both non-self-cytosolic RNA and dsDNA. ERIS (also known as STING or MITA) resided exclusively on ER membrane. The ER retention/retrieval sequence RIR was found to be critical to retain the protein on ER membrane and to maintain its integrity. ERIS was dimerized on innate immune challenges. Coumermycin-induced ERIS dimerization led to strong and fast IFN induction, suggesting that dimerization of ERIS was critical for self-activation and subsequent downstream signaling.

• NN
  National Natural Science Foundation of China

  Award: 30772024
• CA
  Chinese Academy of Sciences
• SI
  Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
• DF
  Directorate for Biological Sciences
• NK
  National Key Research and Development Program of China