OTUD7B通过对TRAF3进行二基化来控制非正规NF-κB激活
Hongbo Hu1, George C Brittain, Jae-Hoon Chang
1Department of Immunology, The University of Texas MD Anderson Cancer Center, 7455 Fannin Street, Box 902, Houston, Texas 77030, USA.
Nature
|January 22, 2013
概括
双基因酶OTUD7B通过稳定TRAF3.3来调节非正规NF-κB通路. OTUD7B 缺乏导致免疫过度激活,影响B细胞反应和对病原体的宿主防御.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
背景情况:
- 非正规的NF-κB通路对免疫功能至关重要,如淋巴细胞细胞生成和B细胞活性.
- 激活需要TNF受体相关因子3 (TRAF3) 降解,但其调节仍然不清楚.
研究的目的:
- 为了确定非正规NF-κB通路的调节者.
- 阐明OTUD7B在控制TRAF3稳定性和通路激活中的作用.
主要方法:
- 使用了具有OTUD7B缺陷的小鼠模型.
- 研究了NF-κB通路的激活,TRAF3的无化和降解.
- 评估B细胞反应和宿主防御机制.
主要成果:
- OTUD7B 缺乏导致非正规NF-κB通路的过度激活,而不会影响正规通路.
- OTUD7B直接与TRAF3结合和脱,抑制其蛋白解.
- 缺少OTUD7B的小鼠表现出B细胞的高反应性和对Citrobacter rodentium的增强抵抗力.
结论:
- OTUD7B 是一个关键的二维基因酶,通过稳定 TRAF3.3 来控制非正规的 NF-κB 信号.
- OTUD7B作为免疫反应的关键负调节剂,防止异常激活.
- 这项研究揭示了一种通过OTUD7B介导的TRAF3二维基因化进行免疫调节的新机制.
更多相关视频
相关概念视频
Co-activators and Co-repressors
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...
Master Transcription Regulators
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...
NF-κB-dependent Signaling Pathway
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 heterodimer of NF-κB...
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Receptor Downregulation in MVBs
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 activation may...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
TGF - β Signaling Pathway
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 are of three kinds RI, RII, and RIII. The RI...
NF-kB-dependent Signaling Pathway
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 heterodimer of NF-κB...
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...


