UFL1 promotes antiviral immune response by maintaining STING stability independent of UFMylation.

UFL1 promotes antiviral immune response by maintaining STING stability independent of UFMylation.
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UFL1 通过独立于 UFMylation 维持 STING 稳定性来促进抗病毒免疫反应

DOI:
10.1038/s41418-022-01041-9
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发表时间:
2023-01
影响因子:
12.4
通讯作者:
Yu, Yizhi
Yu, Yizhi
中科院分区:
生物学1区
文献类型:
--
作者:
Tao, Yijie;Yin, Shulei;Liu, Yang;Li, Chunzhen;Chen, Yining;Han, Dan;Huang, Jingyi;Xu, Sheng;Zou, Zui;Yu, Yizhi

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STING稳态的精确调节对其抗病毒功能至关重要。翻译后修饰,尤其是泛素化,对于STING稳态的调节是重要的。以前的研究主要集中在STING是如何降解的,但对其维持知之甚少。在这里,我们表明UFM 1特异性连接酶UFL 1通过维持STING表达独立于UFMylation来促进先天免疫应答。在机制上,UFL 1抑制TRIM 29与STING相互作用,从而减少其在K338/K347/K370处的泛素化和随后的蛋白酶体降解。DNA病毒感染降低UFL 1表达,这可能促进STING降解并促进病毒扩增。我们的研究确定UFL 1是维持STING稳定性和抗病毒功能的关键调节因子,并为DNA病毒的免疫逃逸机制提供了新的见解。
The precise regulation of STING homeostasis is essential for its antiviral function. Post-translational modification, especially ubiquitination, is important for the regulation of STING homeostasis. Previous studies have focused on how STING is degraded, but little is known about its maintenance. Here, we show that UFM1 specific ligase UFL1 promotes innate immune response by maintaining STING expression independent of UFMylation. Mechanistically, UFL1 inhibits TRIM29 to interact with STING, thereby reducing its ubiquitination at K338/K347/K370 and subsequent proteasomal degradation. DNA virus infection reduces the UFL1 expression, which may promote STING degradation and facilitate viral expansion. Our study identifies UFL1 as a crucial regulator for the maintenance of STING stability and antiviral function, and provides novel insights into the mechanistic explanation for the immunological escape of DNA virus.
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