一个NIK-SIX信号轴通过针对性地静止非正规NF-κB来控制炎症
Zixu Liu1, Katrina B Mar1, Natasha W Hanners2
1Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Nature
|March 22, 2019
概括
非正规的NF-κB途径调节免疫力和发育. 研究人员发现,由NIK重新激活的SIX1和SIX2转录因子控制炎症基因表达和反.
科学领域:
- 免疫学
- 分子生物学
- 细胞信号传输
背景情况:
- 非正规的NF-κB途径对免疫反应和发育至关重要,但其转录调节的理解不足.
- 在这种途径中,NF-κB诱导激酶 (NIK) 是限制速率的酶.
- 失调与免疫疾病和癌症有关.
研究的目的:
- 研究非正规NF-κB通路的转录调节机制.
- 确定这种信号级联的新组件和调节器.
- 探索SIX1和SIX2在免疫反应和疾病中的作用.
主要方法:
- 研究了SIX1和SIX2在非正规NF-κB途径中的作用.
- 使用NIK介导的无素蛋白酶路径来重新激活SIX蛋白质.
- 分析了SIX1和SIX2的炎症基因促进剂和与RELA/RELB的相互作用.
- 评估SIX1在内毒性休克和癌症的小鼠模型中的影响.
主要成果:
- SIX1和SIX2被确定为非正规NF- kB途径的组成部分.
- 通过抑制无素蛋白酶路径,NIK在巨细胞中重新激活SIX蛋白质.
- SIX1和SIX2直接抑制RELA和RELB,形成一个负反循环.
- 在小鼠中,SIX1抑制了炎症并有助于恢复.
- SIX1和SIX2保护了肺癌细胞免受化疗引起的死亡.
结论:
- 一个新的NIK-SIX信号轴微调炎症基因表达.
- 这一轴在生理免疫和癌症等病理疾病中起着至关重要的作用.
- SIX 蛋白代表炎症性疾病和癌症的潜在治疗点.
相关概念视频
01:41Non-Canonical Wnt Signaling Pathways
8.4K
Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
8.4K
02:26NF-κB-dependent Signaling Pathway
10.0K
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...
10.0K
02:54Canonical Wnt Signaling Pathway
10.6K
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
10.6K
01:38Inflammation
62.0K
Overview
62.0K
01:37Hypothalamic-Pituitary Axis
65.9K
The response to stress—be it physical or psychological, acute or chronic—involves activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis. The HPA axis is part of the neuroendocrine system because it involves both neuronal and hormonal communication. Its function is to regulate homeostatic systems—metabolic, cardiovascular, and immune—providing the necessary means to respond to a stressor.
65.9K
01:16Perpendicular-Axis Theorem
4.5K
The perpendicular-axis theorem states that the moment of inertia of a planar object about an axis perpendicular to its plane is equal to the sum of the moments of inertia about two mutually perpendicular concurrent axes lying in the plane of the body.
Consider a circular disc of mass M and radius R lying along an x-y plane. The origin lies at the center of the disc, and the z-axis is perpendicular to the disc's plane. All three axes coincide at the disc's center. The moment of inertia of this...
Consider a circular disc of mass M and radius R lying along an x-y plane. The origin lies at the center of the disc, and the z-axis is perpendicular to the disc's plane. All three axes coincide at the disc's center. The moment of inertia of this...
4.5K