增加蛋白质体活动以改变XBP1信号的UPR通路
Kate A Kragness1,2, Darci J Trader1,2,3
1Department of Pharmaceutical Sciences, University of California, Irvine, California, USA.
Chembiochem : a European journal of chemical biology
|January 31, 2026
概括
小分子蛋白酶激活剂可以减少未折叠蛋白质响应 (UPR) 信号传递,如果在内分泌网膜 (ER) 应激之前给予. 然而,它们不会影响正在进行的UPR,这表明干预的关键时间窗口.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生物化学
- 分子生物学分子生物学
背景情况:
- 增强的蛋白酶体活动赋予了抵抗细胞压力的能力.
- 蛋白酶组分的基因上调是实现这一目标的常见方法.
- 小分子蛋白酶激活剂在调节应激反应,特别是未折叠蛋白质反应 (UPR) 中的作用仍然不太清楚.
研究的目的:
- 调查小分子20S蛋白酶激活剂是否可以调节IRE1驱动的UPR.期间X盒结合蛋白1 (XBP1) 信号传递.
- 为了确定蛋白酶激活剂对UPR激活的时间效应.
主要方法:
- 使用小分子20S蛋白酶激活剂.
- 使用化学剂诱导IRE1驱动的未折叠蛋白反应 (UPR).
- 在UPR诱导之前或之后服用蛋白酶激活剂.
- 评估了对XBP1信号传输的影响.
主要成果:
- 在IRE1诱导之前,使用20S蛋白酶激活剂进行预处理显著减弱了XBP1信号传递.
- 在IRE1的化学诱导后,用蛋白酶激活剂治疗对XBP1信号传递没有可检测的影响.
- 这些发现表明,蛋白质酶激活剂可以在ER压力下增强蛋白质酶功能,但其改变已建立的UPR的能力有限.
结论:
- 小分子蛋白酶激活剂可以在内 плазма网膜 (ER) 应激过程中增强蛋白酶活性.
- 蛋白酶激活剂调节正在进行的UPR的能力有限,突出显示了它们治疗潜力的关键时间窗口.
- 这项研究提供了对蛋白酶激活对应激适应信号通路的时间依赖影响的见解.
相关概念视频
02:18The Proteasome
10.2K
Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
10.2K
03:14Notch Signaling Pathway
6.6K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
6.6K
02:33Hedgehog Signaling Pathway
10.1K
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
10.1K
01:19Interactions Between Signaling Pathways
7.4K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.4K
01:41Non-Canonical Wnt Signaling Pathways
8.5K
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...
8.5K
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