Interaction mapping of endoplasmic reticulum ubiquitin ligases identifies modulators of innate immune signalling
Interaction mapping of endoplasmic reticulum ubiquitin ligases identifies modulators of innate immune signalling
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内质网泛素连接酶的相互作用图谱鉴定了先天免疫信号的调节剂
DOI：
10.1101/2020.03.18.993998
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Fenech E
中科院分区：
文献类型：
--
作者：
Fenech E
嵌入内质网（ER）膜的泛素连接酶（E3）调节基本的细胞活动，包括蛋白质质量控制，钙流量和固醇稳态。至少有25种不同的，跨膜结构域（TMD）的E3预测是ER定位，但对于大多数人来说，他们的组织和细胞的作用仍然很难定义。使用比较蛋白质组学工作流程，我们绘制了21个稳定表达的全长E3的450多个蛋白质-蛋白质相互作用。生物信息学分析将ER-E3及其相互作用物与多种稳态、调节和代谢途径联系起来。其中有四个膜包埋的相互作用RNF 26，多位E3的丰度是自动调节的泛素-蛋白酶体依赖性降解。RNF 26与TMEM 43、ENDOD 1、TMEM 33和TMED 1共组装以形成能够通过cGAS-STING途径调节先天免疫信号传导的复合物。这种RNF 26复合物代表了ER膜上STING和先天免疫信号传导的新调节轴。总的来说，这些数据揭示了ER-E3介导的膜系和细胞质过程的广泛调节和差异功能。
Ubiquitin ligases (E3s) embedded in the endoplasmic reticulum (ER) membrane regulate essential cellular activities including protein quality control, calcium flux, and sterol homeostasis. At least 25 different, transmembrane domain (TMD)-containing E3s are predicted to be ER-localised, but for most their organisation and cellular roles remain poorly defined. Using a comparative proteomic workflow, we mapped over 450 protein-protein interactions for 21 stably expressed, full-length E3s. Bioinformatic analysis linked ER-E3s and their interactors to multiple homeostatic, regulatory, and metabolic pathways. Among these were four membrane-embedded interactors of RNF26, a polytopic E3 whose abundance is auto-regulated by ubiquitin-proteasome dependent degradation. RNF26 co-assembles with TMEM43, ENDOD1, TMEM33 and TMED1 to form a complex capable of modulating innate immune signalling through the cGAS-STING pathway. This RNF26 complex represents a new modulatory axis of STING and innate immune signalling at the ER membrane. Collectively, these data reveal the broad scope of regulation and differential functionalities mediated by ER-E3s for both membrane-tethered and cytoplasmic processes.
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影响因子：
16
作者：
Das, Ranabir;Mariano, Jennifer;Tsai, Yien Che;Kalathur, Ravi C.;Kostova, Zlatka;Li, Jess;Tarasov, Sergey G.;McFeeters, Robert L.;Altieri, Amanda S.;Ji, Xinhua;Byrd, R. Andrew;Weissman, Allan M.
通讯作者：
Weissman, Allan M.
影响因子：
7
作者：
Huelsmann, Julia;Kravic, Bojana;Meyer, Hemmo
通讯作者：
Meyer, Hemmo
影响因子：
21.3
作者：
Gyrd-Hansen, Mads;Darding, Maurice;Miasari, Maria;Santoro, Massimo M.;Zender, Lars;Xue, Wen;Tenev, Tencho;da Fonseca, Paula C. A.;Zvelebil, Marketa;Bujnicki, Janusz M.;Lowe, Scott;Silke, John;Meier, Pascal
通讯作者：
Meier, Pascal
影响因子：
8.8
作者：
Shoulders MD;Ryno LM;Genereux JC;Moresco JJ;Tu PG;Wu C;Yates JR 3rd;Su AI;Kelly JW;Wiseman RL
通讯作者：
Wiseman RL
影响因子：
7.7
作者：
Sam A. Menzies;Norbert Volkmar;D. J. van den Boomen;R. Timms;Anna S Dickson;J. Nathan;P. Lehner
通讯作者：
Sam A. Menzies;Norbert Volkmar;D. J. van den Boomen;R. Timms;Anna S Dickson;J. Nathan;P. Lehner