相关实验视频
Updated: Jun 21, 2026

08:33
Ubiquitin Chain Analysis by Parallel Reaction Monitoring
Published on: June 17, 2020
通过未固的多比基链直接激活蛋白质激酶
Zong-Ping Xia1, Lijun Sun, Xiang Chen
1Department of Molecular Biology, University of Texas, Southwestern Medical Center, Dallas, Texas 75390-9148, USA.
Nature
|August 14, 2009
概括
没有固的多比基因链直接激活TAK1和IKK激酶,而不依赖于蛋白的修饰. 这一发现揭示了关键信号通路中蛋白激酶调节的新机制.
科学领域:
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
- 在Ubiquitination中使用.
背景情况:
- 对于通过IL-1R和Toll类受体通路激活NF-kappaB和MAP激酶至关重要的是TRAF6 (E3泛基因酶).
- 与UBC13/UEV1A一起的TRAF6形成了与Lys 63结合的多联链,激活TAK1激酶复合体,然后激活IKK和NF-kappaB.
- 蛋白质在TAK1和IKK激活中的作用仍然不清楚.
研究的目的:
- 调查特定蛋白质的无处不在是否对于TAK1或IKK激活至关重要.
- 阐明TAK1和IKK激活的直接机制,以响应无处不在信号.
主要方法:
- 使用纯化蛋白质在体外复制TAK1激活.
- 在TAK1激活中分析自由Lys 63聚比基链的作用.
- 在IKK激活过程中,研究由TRAF6和UBCH5C合成的无聚基因链.
- 对TAK1和IKK激活的二基化酶活性的评估.
主要成果:
- 免费的Lys 63聚基因链通过与基因受体TAB2结合,直接激活TAK1,从而导致TAK1自酸化和激活.
- 由TRAF6和UBCH5C合成的无聚基链激活了IKK复合体.
- 通过duebiquitination酶废除TAK1和IKK激活,分解聚比基链.
结论:
- 没有固的多比基因链,没有与标蛋白结合,直接激活TAK1和IKK.
- 这项研究揭示了一种由自由聚比基因链介导的蛋白质激酶调节的新机制.
- 研究结果表明,在超出基质修饰的信号传导中,无处不在的作用具有直接作用.
相关概念视频
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...
Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
The Proteasome
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 (ubiquitin...
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 (ubiquitin...
The Proteasome
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...
Amplifying Signals via Enzymatic Cascade
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
Protein Kinases and Phosphatases
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...

