| Autor: |
Dapei Li, Rongsheng Wu, Wen Guo, Lifen Xie, Zigang Qiao, Shengchuan Chen, Jingfei Zhu, Chaohao Huang, Jian Huang, Bicheng Chen, Yanghua Qin, Feng Xu, Feng Ma |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 29, Iss 5, Pp 1249-1260.e4 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2019.09.069 |
| Popis: |
Summary: γ-interferon-inducible protein-16 (IFI16), a key DNA sensor, triggers downstream STING-dependent type I interferon (IFN-I) production and antiviral immunity. However, it is still unclear how to negatively regulate IFI16 to avoid excessive IFN-I production and autoimmunity. Here, we find that STING directly interacts with IFI16 and facilitates IFI16 degradation via the ubiquitin-proteasome pathway by recruiting the E3 ligase TRIM21. The 1-pyrin region of IFI16 is responsible for the IFI16-STING interaction, and the first three lysines in the N-terminal region of IFI16 are the key sites that lead to STING-mediated IFI16 ubiquitination and degradation. Compared to wild-type IFI16, a higher level of viral DNA triggered IFN-β and antiviral IFN-stimulated gene expression, and thus less HSV-1 infection, was observed in the cells transfected with IFI16-K3/4/6R, an IFI16 mutant that is resistant to degradation. STING-mediated negative feedback regulation of IFI16 restricts IFN-I overproduction during antiviral immunity to avoid autoimmune diseases. : Li et al. show that STING mediates negative feedback regulation of IFI16 and restricts type I IFN overproduction during immune responses to viruses such as HSV-1. Keywords: IFI16, STING, DNA sensor, E3 ligase, ubiquitin proteasome system, type I interferon, IFN-stimulated gene, antiviral immunity |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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