ABIN-1是一种泛素传感器,可以限制细胞死亡并维持胚胎发育
Shigeru Oshima1, Emre E Turer, Joseph A Callahan
1Department of Medicine, University of California at San Francisco, 513 Parnassus Avenue, S-1057, San Francisco, California 94143-0451, USA.
Nature
|December 9, 2008
概括
ABIN-1蛋白质缺乏导致胚胎死亡,通过增加对瘤死因子 (TNF) 诱导的细胞死亡的敏感性. 在ABIN-1中使用.
科学领域:
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
- 发展生物学 发展生物学
背景情况:
- 瘤亡因子受体 (TNFR) 信号蛋白对于细胞激活和存活至关重要.
- ABIN-1 (A20结合剂和NF-kappaB抑制剂) 是一种涉及抑制NF-kappaB信号传递的蛋白质.
研究的目的:
- 研究ABIN-1在胚胎发育和细胞存活中的体内功能.
- 阐明ABIN-1调节瘤亡因子 (TNF) 诱导的编程细胞死亡的机制.
主要方法:
- 产生和分析ABIN-1缺乏的小鼠.
- 评估细胞对TNF诱导的亡的敏感性.
- 研究ABIN-1在TNF信号复合体和caspase 8招募中的作用.
- 分析ABIN-1与多比基链的相互作用.
主要成果:
- 缺乏ABIN-1的小鼠由于胎儿肝脏亡,贫血和低成形而表现出胚胎致死性.
- 缺少ABIN-1的细胞对TNF诱导的编程细胞死亡过敏,TNF缺乏可以挽救.
- 在TNF信号复合体中,ABIN-1抑制了酶8对FADD的招募,从而防止了亡.
- ABIN-1的抗亡活性取决于它结合聚比基链的能力.
结论:
- ABIN-1对于胚胎的生存至关重要,它调节TNF诱导的亡.
- 通过聚比基结合,ABIN-1通过阻止酶8的激活而起作用.
- 这些发现凸显了在生物的生存中,无处化和无处感应的关键作用.
相关概念视频
Negative Regulator Molecules
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
Cellular Injury V: Apoptosis and Autophagy
Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
Regulated Protein Degradation
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
The Spindle Assembly Checkpoint
The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
Anaphase Promoting Complex
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
Regulation of the Unfolded Protein Response
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...


