丹麦奥尔胡斯大学Sren R. Paludan研究团队在研究中取得进展。他们探明了STEEP介导STING 出内质网（ER）并激活信号。相关论文发表在2020年7月20日的《自然-免疫学》杂志上。

研究人员发现STEEP是STING信号的正调控因子。STEEP与STING有关，并促进了其在ER的运输。这是通过诱导磷脂酰肌醇-3-磷酸（PtdIns（3）P）的产生和ER膜曲率形成实现的，从而引起COPII调控的STING从ER到高尔基体的运输。STEEP缺失会损害STING相关疾病患者脑组织和细胞中的病毒感染，从而削弱了STING诱导的基因表达。有趣的是，来自患者STING功能获得的突变体与STEEP强烈相互作用，从而导致ER PtdIns（3）P水平和膜曲率增加。因此，STEEP通过促进STING出ER来激活此信号通路。

据了解，STING对于预防感染和进行肿瘤免疫监控必不可少，但它也可以诱发病理性炎症。STING驻留在ER上，并在刺激后发生信号传导实现ERGIC /高尔基体上运输。尽管STING 出ER是STING信号通路中的限速步骤，但诱发此过程的机制尚不清楚。

附：英文原文

Title: STEEP mediates STING ER exit and activation of signaling

Author: Bao-cun Zhang, Ramya Nandakumar, Line S. Reinert, Jinrong Huang, Anders Laustsen, Zong-liang Gao, Cheng-long Sun, Sren Beck Jensen, Anne Troldborg, Sonia Assil, Martin F. Berthelsen, Carsten Scavenius, Yan Zhang, Samuel J. Windross, David Olagnier, Thaneas Prabakaran, Chiranjeevi Bodda, Ryo Narita, Yujia Cai, Cong-gang Zhang, Harald Stenmark, Christine M. Doucet, Takeshi Noda, Zheng Guo, Raphaela Goldbach-Mansky, Rune Hartmann, Zhijian J. Chen, Jan J. Enghild, Rasmus O. Bak, Martin K. Thomsen, Sren R. Paludan

Issue&Volume: 2020-07-20

Abstract: STING is essential for control of infections and for tumor immunosurveillance, but it can also drive pathological inflammation. STING resides on the endoplasmic reticulum (ER) and traffics following stimulation to the ERGIC/Golgi, where signaling occurs. Although STING ER exit is the rate-limiting step in STING signaling, the mechanism that drives this process is not understood. Here we identify STEEP as a positive regulator of STING signaling. STEEP was associated with STING and promoted trafficking from the ER. This was mediated through stimulation of phosphatidylinositol-3-phosphate (PtdIns(3)P) production and ER membrane curvature formation, thus inducing COPII-mediated ER-to-Golgi trafficking of STING. Depletion of STEEP impaired STING-driven gene expression in response to virus infection in brain tissue and in cells from patients with STING-associated diseases. Interestingly, STING gain-of-function mutants from patients interacted strongly with STEEP, leading to increased ER PtdIns(3)P levels and membrane curvature. Thus, STEEP enables STING signaling by promoting ER exit.

DOI: 10.1038/s41590-020-0730-5

Source: https://www.nature.com/articles/s41590-020-0730-5