高通量选E3泛素酶确定TRIM48作为RIG-I信号传输的新型负调节器
Guandi Wu1, Jamie Frankish2, Joschka Willemsen3
1Research Group "Dynamics of Early Viral Infection and the Innate Antiviral Response", Division Virus-Associated Carcinogenesis (D430), German Cancer Research Center (DKFZ), Heidelberg, Germany; Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany.
Cellular signalling
|July 3, 2025
概括
这项研究选了E3泛素酶,并发现TRIM48作为视网膜酸诱导基因-I (RIG-I) 信号的负调节器,控制抗病毒免疫力.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 病毒学 病毒学
背景情况:
- 网红酸诱导基因-I (RIG-I) 信号传递对先天性抗病毒免疫至关重要,启动细胞因子的产生.
- 严格调节RIG-I对于防止有害宿主反应至关重要.
研究的目的:
- 系统地选E3无素连接酶,以确定它们在调节RIG-I信号传输中的作用.
- 为了确定RIG-I路径的新型调节者.
主要方法:
- 使用活细胞成像试验进行了616E3泛素酶的高通量siRNA查,以监测IRF3和NF-κB核转位.
- 候选人验证涉及第二次选,评估对裂谷热病报告病毒和IFN-β促进剂活性测定的抗病毒反应.
主要成果:
- 十四个E3泛素酶一致影响了RIG-I在两个屏幕上的信号传输.
- TRIM48被确定为一个强大的负调节剂,抑制RIG-I激活,IFN产生,并在过度表达时增强病毒复制.
- TRIM48 缺陷增强了 RIG-I 信号传递和抗病毒反应,作为一个依赖于其酶活性的诱导反调节器.
结论:
- 这项研究提供了涉及RIG-I信号传递的E3泛素酶的全面选.
- TRIM48被确定为RIG-I通路的关键负反调节器,对控制抗病毒免疫力至关重要.
相关概念视频
PI3K/mTOR/AKT Signaling Pathway
4.0K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
4.0K
Regulation of the Unfolded Protein Response
2.6K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.6K
Negative Regulator Molecules
36.1K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
36.1K
mTOR Signaling and Cancer Progression
3.9K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.9K


