通过与MEK的相互作用,SARS-CoV-2 NSP14诱导AP-1的转录活性
Weiling Li1, Yuansong Wang1, Qian Peng1
1Hubei Key Laboratory of Cognitive and Affective Disorders, Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan, China.
Molecular immunology
|September 12, 2024
概括
SARS-CoV-2 NSP14 蛋白质通过促进细胞因子生产来激活宿主免疫反应. 它通过与MEK相互作用并激活ERK/AP-1通路来实现这一目标,从而导致炎症.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 众所周知,SARS-CoV-2的NSP14蛋白对于病毒复制至关重要.
- 新出现的证据表明NSP14也会影响宿主免疫系统,特别是细胞因子的产生.
研究的目的:
- 阐明SARS-CoV-2 NSP14蛋白激活宿主免疫系统的机制.
- 为了确定涉及NSP14介导免疫激活的特定分子通路和蛋白质相互作用.
主要方法:
- 研究了通过NSP14激活激活蛋白1 (AP-1) 途径的激活.
- 评估了细胞外信号调节激酶 (ERK) 的酸化及其核转位.
- 选了NSP14与ERK通路中的关键蛋白之间的相互作用,包括MEK.
- 利用MEK抑制剂U0126来评估其对NSP14诱导信号传递的影响.
- 研究了NSP14的EXON域在MEK相互作用和激活中的作用.
主要成果:
- 通过增加ERK酸化 (p-ERK),NSP14显著激活了AP-1通路.
- 发现NSP14与MEK,ERK上游的一个激酶相互作用,增加MEK酸化.
- 用U0126抑制MEK降低了NSP14诱导的p-ERK,并部分阻止了细胞因子的产生.
- NSP14的ExoN域被确定为MEK相互作用和激活的关键.
- 这些发现表明NSP14激活MEK以增强AP-1信号,从而导致细胞因子的产生.
结论:
- 通过MEK/ERK/AP-1信号通路,SARS-CoV-2 NSP14蛋白激活了一种促炎反应.
- NSP14的EXON域对于与MEK的相互作用和激活至关重要,这是免疫激活过程中的关键步骤.
- 这项研究揭示了涉及免疫系统调节的SARS-CoV-2病变发生的新型机制.
关键词:
AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1炎症 炎症是一种炎症.在NSP14中,我们可以使用NSP14.英国空军/MEK/ERKK这就是SARS-CoV-2病毒.更多相关视频
相关概念视频
MAPK Signaling Cascades
5.3K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.3K
cAMP-dependent Protein Kinase Pathways
6.2K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
6.2K
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
NF-κB-dependent Signaling Pathway
7.4K
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...
7.4K
Master Transcription Regulators
6.9K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.9K
PI3K/mTOR/AKT Signaling Pathway
3.4K
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...
3.4K


