Regulation of an adaptor protein STING by Hsp90β to enhance innate immune responses against microbial infections
Regulation of an adaptor protein STING by Hsp90β to enhance innate immune responses against microbial infections
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DOI：
10.1016/j.cellimm.2020.104188
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发表时间：
2020-10-01
影响因子：
4.3
通讯作者：
Takaoka, Akinori
中科院分区：
文献类型：
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作者：
Sato, Seiichi;Li, Kai;Takaoka, Akinori
干扰素基因刺激物(STING)在DNA介导的天然免疫反应中起着重要作用。然而，从稳定的角度来看，刺痛的调节机制还不完全清楚。在此，我们鉴定了伴侣蛋白Hsp90是一种新的刺激性相互作用蛋白。用Hsp90抑制剂17-AAG处理和敲除Hsp90β而不是Hsp90α在蛋白质水平上减少了刺痛，导致了对cGAMP刺激的干扰素诱导的抑制，以及HSV-1和单核细胞增生性李斯特菌的感染。综上所述，我们的结果表明，Hsp90β对刺蛋白的控制是DNA传感途径中的一个关键生物学过程。
Stimulator of interferon genes (STING) plays important roles in the DNA-mediated innate immune responses. However, the regulatory mechanism of STING in terms of stabilization is not fully understood. Here, we identified the chaperone protein Hsp90s as novel STING interacting proteins. Treatment with an Hsp90 inhibitor 17-AAG and knockdown of Hsp90 beta but not Hsp90 alpha reduced STING at protein level, resulted in the suppression of IFN induction in response to stimulation with cGAMP, and infections with HSV-1 and Listeria monocytogenes. Collectively, our results suggest that the control of STING protein by Hsp90 beta is a critical biological process in the DNA sensing pathways.