Division of Signaling in Cancer and Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido 060-0815, Japan; Molecular Medical Biochemistry Unit, Biological Chemistry and Engineering Course, Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo, Hokkaido 060-0815, Japan.
Division of Signaling in Cancer and Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido 060-0815, Japan; Molecular Medical Biochemistry Unit, Biological Chemistry and Engineering Course, Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo, Hokkaido 060-0815, Japan.
Cell Immunol. 2020 Oct;356:104188. doi: 10.1016/j.cellimm.2020.104188. Epub 2020 Jul 28.
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 Hsp90β but not Hsp90α 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 Hsp90β is a critical biological process in the DNA sensing pathways.
干扰素基因刺激物 (STING) 在 DNA 介导的先天免疫反应中发挥重要作用。然而，STING 稳定性的调节机制尚不完全清楚。在这里，我们鉴定了伴侣蛋白 HSP90s 是 STING 的新型相互作用蛋白。用 HSP90 抑制剂 17-AAG 处理和敲低 HSP90β而不是 HSP90α 会降低蛋白水平的 STING，导致 cGAMP 刺激和 HSV-1 和李斯特菌感染时 IFN 诱导的抑制。总之，我们的结果表明，HSP90β 对 STING 蛋白的控制是 DNA 感应途径中的一个关键生物学过程。
