A protein-interaction network of interferon-stimulated genes extends the innate immune system landscape

A protein-interaction network of interferon-stimulated genes extends the innate immune system landscape
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DOI:
10.1038/s41590-019-0323-3
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发表时间:
2019-04-01
期刊:
影响因子:
30.5
通讯作者:
Pichlmair, Andreas
Pichlmair, Andreas
中科院分区:
医学1区
文献类型:
--
作者:
Hubel, Philipp;Urban, Christian;Pichlmair, Andreas

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干扰素刺激基因(ISGs)是先天免疫系统的骨干,对限制细胞内和细胞间病毒复制和传播具有重要作用。我们进行了一项基于质谱的调查,以了解先天免疫系统的基本组织,并探索单个isg的分子功能。我们确定了104个isg和1,401个细胞结合伙伴之间的相互作用,参与了2,734个高可信度相互作用。到目前为止,这些相互作用中有90%未被报道,因此我们的调查揭示了比目前已知的更广泛的isg活动范围。将由此产生的isg相互作用网络与已发表的数据集和功能研究相结合,使我们能够确定免疫调节因子和与免疫系统相关的过程。鉴于先天免疫系统的异常健壮性,这种ISG网络可以作为细胞系统治疗靶向的蓝图,以有效地对抗病毒感染。
Interferon-stimulated genes (ISGs) form the backbone of the innate immune system and are important for limiting intra- and intercellular viral replication and spread. We conducted a mass-spectrometry-based survey to understand the fundamental organization of the innate immune system and to explore the molecular functions of individual ISGs. We identified interactions between 104 ISGs and 1,401 cellular binding partners engaging in 2,734 high-confidence interactions. 90% of these interactions are unreported so far, and our survey therefore illuminates a far wider activity spectrum of ISGs than is currently known. Integration of the resulting ISG-interaction network with published datasets and functional studies allowed us to identify regulators of immunity and processes related to the immune system. Given the extraordinary robustness of the innate immune system, this ISG network may serve as a blueprint for therapeutic targeting of cellular systems to efficiently fight viral infections.