クリン-RINGのユビキチンリガースネットワークの動態は,体系的な定量プロテオミクスによって明らかになりました
Eric J Bennett1, John Rush, Steven P Gygi
1Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Cell
|December 15, 2010
まとめ
この研究は,クリン・リング・ユビキチン・リゲーゼ (CRL) ネットワークの組織が主にアダプタモジュールの豊富さによって動かされ,ネディレーションやCAND1結合サイクルによって動かされないことを明らかにしています. 定量プロテオミクスは,CRL複合改造の既存のモデルに挑戦しています.
科学分野:
- バイオケミストリー バイオケミストリー
- 分子生物学は分子生物学である.
- プロテオミクス プロテオミクスは,プロテオミクスの
背景:
- 信号システムの再編成は,経路の乱れの間に一般的です.
- 経路刺激によるネットワークの再構築に関する定量的な研究は稀である.
- Cullin-RINGユビキチンリガゼ (CRL) 複合体は,細胞の調節に中心的な役割を果たしています.
研究 の 目的:
- CRLネットワークアーキテクチャを明らかにするための定量プロテオミクスプラットフォームを開発する.
- 動的CRL改造の現在のモデルを評価する.
- CRL複合調節におけるネディレーションとCAND1結合の役割を調査する.
主な方法:
- マルチプレックス絶対定量化 (AQUA) テクノロジーを用いた定量プロテオミクスプラットフォームの開発.
- NEDD8活性化酵素の阻害剤であるMLN4924を用いたCRL複合体の急性阻害.
- CRLの複合ステキオメトリーとサブユニット関連の分析.
主要な成果:
- 急性CRL阻害は,世界的なCRLネットワークの再編成を誘導しませんでした.
- カリンの有意な割合は,ネディレーション状態に関係なく,アダプターモジュールで組み立てられています.
- カリンのわずかな部分のみがCAND1.1と関連していることが判明しました.
結論:
- NEDDYLATION/CAND1結合サイクルではなく,アダプターモジュールの豊富さは,CRLネットワーク組織の主要なドライバーであるようです.
- CRLの複雑なダイナミシティの現在のモデルは,改定する必要があります.
- 定量プロテオミクスは,複雑な細胞ネットワークの規制に関する新しい洞察を提供します.
関連する概念動画
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.
Protein Networks
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
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These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
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...
The Unfolded Protein Response
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
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 Structure
The ubiquitin-proteasome pathway is a well-known mechanism utilized by eukaryotic cells to remove cytoplasmic proteins that are misfolded, damaged, or no longer needed. In this pathway, the protein that needs to be eliminated undergoes a process called ubiquitination, where a chain of ubiquitin molecules is attached to the 48th lysine residue of the target protein. This ubiquitin modification helps the proteasome distinguish between a target protein and a healthy protein.
The proteasome is an...
The proteasome is an...


