线性无处不在介导着冠状病毒NSP14诱导的NF-κB激活
Fang Hua1, Wenzhuo Hao1, Lingyan Wang2
1Department of Microbiology and Immunology, Tulane University, New Orleans, LA, 70112, USA.
Cell communication and signaling : CCS
|November 30, 2024
概括
冠状病毒劫持了宿主.
科学领域:
- 病毒学和免疫学 病毒学和免疫学
- 分子生物学分子生物学
- 细胞信号传输 细胞信号传输
背景情况:
- 人类冠状病毒导致各种呼吸系统疾病.
- 冠状病毒促进炎症的机制尚未完全理解.
- 了解宿主免疫的病毒操纵对于治疗开发至关重要.
研究的目的:
- 研究冠状病毒非结构蛋白14 (NSP14) 在调节宿主天生的免疫反应中的作用.
- 阐明NSP14引发炎症的机制.
- 为了确定参与NSP14介导免疫激活的特定宿主因素.
主要方法:
- 同免疫沉测试检测蛋白质与蛋白质相互作用.
- 乌比基因化试验用于分析聚比基因链形成.
- 记者基因测试测量NF-κB转录活性.
- 分析促炎性细胞因子和I型干扰素的表达.
主要成果:
- 冠状病毒NSP14直接与HOIL-1相互作用蛋白 (HOIP) 相互作用,HOIP是线性无素链组装复合体 (LUBAC) 的组成部分.
- 通过LUBAC,NSP14被多化,导致NEMO的招募和IKK复合物的激活.
- 由NSP14诱导的NF-κB激活增强了促炎因素的表达,但抑制了I型干扰素的产生.
- 这导致宿主免疫反应倾向于炎症.
结论:
- 冠状病毒NSP14利用宿主LUBAC路径来激活NF-κB信号传递.
- 这种病毒策略通过调节促炎媒介来促进炎症,同时抑制抗病毒反应.
- 这项研究揭示了一种新型病毒启动的线性泛素化途径,驱动NF-κB激活和炎症.
相关概念视频
NF-κB-dependent Signaling Pathway
7.2K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.2K
Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
Co-activators and Co-repressors
7.3K
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
7.3K
Covalently Linked Protein Regulators
6.8K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
6.8K
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
The JAK-STAT Signaling Pathway
8.7K
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...
8.7K


