USP26通过针对TRAF3进行二维基化来抑制I型干扰素信号传输
Cheng-Lan Sheng1, Bang-Dong Jiang1, Chun-Qiu Zhang1
1Department of Clinical Laboratory, Chongming Brach Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, P. R. China.
PloS one
|July 26, 2024
概括
乌比基特异性蛋白酶26 (USP26) 通过调节RLR通路来增强抗病毒免疫力. USP26二基化TRAF3,促进IRF3的激活和对抗病毒感染的宿主防御,如EV71.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 分子生物学分子生物学
背景情况:
- 脱化酶 (DUBs) 通过RLR通路调节先天抗病毒免疫力.
- 对于对抗病毒感染的RLR通路激活,TRAF3是至关重要的.
- 在TRAF3介导的抗病毒反应中,DUBs的具体作用尚不清楚.
研究的目的:
- 调查在RLR信号通路和抗病毒免疫中Ubiquitin特异性蛋白酶26 (USP26) 的功能.
- 阐明USP26在病毒感染期间调节TRAF3活性的机制.
主要方法:
- 在对EV71感染的反应中分析USP26表达.
- USP26敲击实验评估其对抗病毒基因表达和病毒复制的影响.
- 同免疫沉试验以确定USP26-TRAF3相互作用.
- 西方涂抹检测TRAF3无处不在水平.
主要成果:
- EV71感染可以提高USP26的表达.
- USP26 Knockdown增强了IFN-β和ISG的表达,抑制了EV71的复制,并增加了宿主易感性.
- USP26与TRAF3相互作用,减少其K63结合的多基化,促进pIRF3信号传递.
- 缺乏USP26会增加TRAF3的多比基因化.
结论:
- USP26在RLR信号传递和先天抗病毒反应中发挥着关键作用.
- USP26通过对TRAF3进行脱,促进IRF3的激活来促进抗病毒免疫力.
- 这些发现加深了对杜比基因在调节先天抗病毒防御机制中的作用的理解.
更多相关视频
相关概念视频
Regulation of the Unfolded Protein Response
2.4K
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...
2.4K
TGF - β Signaling Pathway
7.3K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.3K
The JAK-STAT Signaling Pathway
8.8K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
8.8K
siRNA - Small Interfering RNAs
16.7K
Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
16.7K
The Unfolded Protein Response
4.5K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
4.5K
Receptor Downregulation in MVBs
2.0K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.0K


