NF-κB信号传递指导一种在先天免疫反应基因中短暂放大的程序
Michael P Ludwig1,2, Jason R Wilson1,2, Matthew D Galbraith1,3,4
1Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
bioRxiv : the preprint server for biology
|March 31, 2025
概括
研究人员发现了一种新机制,称为短暂的特定位点增益 (TSSG),在免疫细胞中产生异染色体DNA (ecDNA). 这一过程有助于解释免疫反应如何在细胞之间变化,有助于宿主防御.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 细胞对病原体的反应依赖于天生的免疫信号通路.
- 天生的免疫表现出细胞对细胞的异质性,但其潜在机制尚未完全理解.
研究的目的:
- 阐明在天生的免疫反应中建立和调节细胞间异质性的机制.
- 确定在病原体接触期间参与免疫基因调节的新途径.
主要方法:
- 研究了因天生的免疫信号而形成的染色体外DNA (ecDNA).
- 利用技术来追踪免疫相关基因位点的短暂的特定位点增长 (TSSG).
- 分析了NF-κB信号传递,特别是转录因子RelA和MCM2在TSSG诱导中的作用.
- 检查了TSSG控制元素的表观遗传调节.
主要成果:
- 描述了一种短暂的特定位点增益 (TSSG) 程序,该程序在先天免疫信号发送时产生免疫相关基因的ecDNA.
- 证明NF-κB激活通过RelA和MCM2招募驱动干扰素受体基因集群的TSSG.
- 表明有针对性地招募RelA或p300可以诱导TSSG.
- 确定RelA和MCM2为6至179个富含天生的免疫反应基因的区域指定TSSG.
结论:
- 通过TSSG调节的ecDNA产生是一种新发现的机制,有助于宿主天生的免疫反应的异质性.
- 这一发现提供了关于细胞如何实现对病原体的多样性反应的见解,增强了宿主防御策略.
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
Diversity in Cell Signaling Responses
6.3K
The physiological function of a cell and cellular communication are outcomes of a range of extrinsic signals, intracellular signaling pathways, and cellular responses. No two cell types express the same repertoire of signaling components. Receptors are highly selective for their cognate ligands, but once activated, they can alter multiple cellular processes such as DNA transcription, protein synthesis, and metabolic activity.
Graded and Abrupt Responses
Some signaling systems generate...
Graded and Abrupt Responses
Some signaling systems generate...
6.3K
Intracellular Signaling Cascades
46.0K
Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
46.0K
The JAK-STAT Signaling Pathway
8.5K
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...
8.5K
Signal Transduction: Overview
8.1K
Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...
Typically, signal transduction involves three...
8.1K
MAPK Signaling Cascades
5.0K
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...
5.0K


