DDI2蛋白酶通过TCF11/NRF1控制胚胎发育和炎症
Monika Nedomova1,2,3, Stefanie Haberecht-Müller4, Sophie Möller4
1Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic, Flemingovo n. 2, 166 10 Prague, Czech Republic.
iScience
|September 27, 2024
概括
酸蛋白酶DDI2对于细胞蛋白质稳定和胚胎发育至关重要. 它的缺失导致发育失败,并触发压力反应,突出DDI2DI.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 发展生物学 发展生物学
背景情况:
- DDI2是一种酸蛋白酶,可以切割聚基化基板.
- 在蛋白质毒性压力时,DDI2激活转录因子TCF11/NRF1 (NFE2L1).
- 这种激活对于维持蛋白质稳定和表达诸如蛋白质组子单元等救援因子至关重要.
研究的目的:
- 为了研究DDI2除的体内和细胞后果.
- 了解DDI2在蛋白质稳定网络和免疫反应中的作用.
主要方法:
- DDI2淘汰赛 (KO) 鼠标模型.
- 使用DDI2替代KO细胞进行细胞研究.
- 在蛋白质毒性压力下胚胎组织和细胞的分子表征.
主要成果:
- DDI2 KO小鼠在E12.5时表现出严重发育失败的胚胎致死性.
- 胚胎显示蛋白酶表达不足,乌比奎丁合物积累和UPR诱导.
- 缺乏DDI2的细胞表现出ISR激活,I型干扰素特征和IFN诱导的增殖信号.
结论:
- DDI2在胚胎发育和细胞蛋白质稳定中起着至关重要的作用.
- DDI2对于维持平衡的免疫反应很重要.
- DDI2的消去会导致蛋白质毒性压力,发育失败和免疫信号的改变.
相关概念视频
TGF - β Signaling Pathway
7.3K
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...
7.3K
Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.1K
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.1K
Canonical Wnt Signaling Pathway
8.7K
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...
8.7K
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
Regulation of Angiogenesis and Blood Supply
2.5K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.5K
Regulation of the Unfolded Protein Response
2.4K
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...
2.4K


