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Updated: Jun 21, 2026

08:33
Ubiquitin Chain Analysis by Parallel Reaction Monitoring
Published on: June 17, 2020
固定されていないポリユビキチン鎖によるタンパク質キナーゼの直接活性化
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
まとめ
固定されていないポリユビキチン鎖は,標的タンパク質の改変とは関係なく,TAK1およびIKKキナーゼを直接活性化します. この発見は,重要なシグナル伝達経路におけるタンパク質キナーゼ調節のための新しいメカニズムを明らかにしています.
科学分野:
- 分子生物学は分子生物学である.
- 細胞シグナル伝達 細胞信号伝達
- ユビキチネーション (Ubiquitination) とは ユビキチネーション (Ubiquitination) とは ユビキチネーション (Ubiquitination) とは
背景:
- TRAF6 (E3ユビキチンリガゼ) は,IL-1RとToll型受容体経路経由でNF-kappaBとMAPキナーゼを活性化するために重要である.
- TRAF6は,UBC13/UEV1Aと共に,Lys 63結合ポリユビキチン鎖を形成し,TAK1キナーゼ複合体を活性化させ,その複合体は IKKとNF-kappaBを活性化させます.
- TAK1とIKKの活性化におけるタンパク質のユビキチネーションの役割は不明でした.
研究 の 目的:
- 特定のタンパク質のユビキチン化がTAK1またはIKKの活性化に不可欠であるかどうかを調査する.
- ユビキチネーション信号への反応としてTAK1とIKKの活性化の直接的なメカニズムを解明する.
主な方法:
- 精製したタンパク質を用いて,TAK1活性化の再構成を in vitro で行う.
- TAK1の活性化における自由なLys63ポリユビキチン鎖の役割の分析.
- IKK活性化において,TRAF6とUBCH5Cによって合成されるアンアンコールされたポリユビキチン鎖の調査.
- TAK1とIKKの活性化に対するデウビキチン化酵素の活性性の評価.
主要な成果:
- フリーライス63ポリユビキチン鎖は,ユビキチン受容体TAB2と結合することでTAK1を直接活性化させ,TAK1の自己リン酸化と活性化につながります.
- TRAF6とUBCH5Cによって合成されたアンコールされていないポリユビキチン鎖は,IKK複合体を活性化させます.
- デウビキチネーション酵素によるポリユビキチン鎖の分解 TAK1とIKKの活性化が取り消された.
結論:
- 標的タンパク質と結合していないアンカリングされていないポリユビキチン鎖は,TAK1とIKKを直接活性化します.
- この研究は,自由ポリユビキチン鎖によって介されるタンパク質キナーゼ調節の新しいメカニズムを明らかにしています.
- 発見は,基板改変を超えて信号伝導におけるユビキチネーションの直接的な役割を示唆しています.
関連する概念動画
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...
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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...

