PARG 调节了 TARG1 的蛋白质体降解
Joséphine Groslambert1, Sara C Buch-Larsen2, Ivo A Hendriks2
1Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Cell reports
|January 7, 2026
概括
多ADP-ribose) 糖酶 (PARG) 通过控制单-ADP-ribose 酶 TARG1.1 的稳定性来调节蛋白质降解. 通过蛋白质酶介导途径,PARG抑制导致TARG1耗尽.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- ADP-ribosylation (ADPr) 是一个关键的翻译后修饰,调节基因组稳定性和细胞应激反应.
- 虽然ADPr转移酶得到了很好的研究,但ADP-ribosyl化酶及其调节作用仍然不明.
- PARG 是逆转ADP-ribosylation的一个关键酶.
研究的目的:
- 研究PARG在蛋白质降解中的功能.
- 为了确定ADP-ribosyl hydrolases的基质和调节机制.
- 探索PARG与其他ADP-ribosylation机制之间的相互作用.
主要方法:
- 定量蛋白质组学用于评估在PARG抑制后蛋白质水平的变化.
- 生物化学测试以确认PAR和蛋白酶体依赖性降解.
- 识别参与该过程的E3泛素连接酶.
主要成果:
- 抑制PARG会导致TARG1蛋白水平的降低.
- TARG1的降解依赖于ADP-ribosylation和蛋白质组.
- 鉴定出HUWE1和TRIP12为介导TARG1降解的E3泛基因酶.
- TARG1是PAR-依赖蛋白质降解的基质.
结论:
- 通过控制TARG1的稳定性,PARG在调节蛋白质降解方面发挥作用.
- 发现了一种新的TARG1降解的PARG-依赖机制.
- 这项研究揭示了PARG和TARG1之间的相互作用,这对针对PARG的治疗策略有影响.
相关概念视频
02:58Regulated Protein Degradation
8.7K
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...
8.7K
02:58Regulated Protein Degradation
3.1K
3.1K
01:13The Proteasome
1.6K
Eukaryotic cells can degrade proteins through several pathways. One of the most important among 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. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
1.6K
02:18The Proteasome
10.0K
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...
10.0K
02:18The Proteasome
4.4K
4.4K
01:22PI3K/mTOR/AKT Signaling Pathway
5.3K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
5.3K