ユビキチンのような改変のプロファイリングは,ミトーシス制御の特徴を明らかにします
Yifat Merbl1, Phillipe Refour, Hevan Patel
1Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Warren Alpert 536, Boston, MA 02115, USA.
Cell
|March 5, 2013
まとめ
この研究では,ユビキチンおよび関連するタンパク質の改変をプロファイルし,それぞれの異なる機能を明らかにし,1500のターゲットを特定しました. FAT10は細胞分裂の調節に重要な役割を果たしていることが示されています.
科学分野:
- バイオケミストリーと分子生物学
- 細胞生物学 細胞生物学
- 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:
- ウビキチンとウビキチン類 (Ubl) の改変は,タンパク質の安定性,活性,および局所化を調節する.
- 多くのUbl改変の正確な機能は,まだ完全に理解されていない.
- これらの変化を理解することは,細胞のプロセスを解読する上で極めて重要です.
研究 の 目的:
- ミトーシス中のウビキチンおよび他の6つのUBLのタンパク質標的を包括的にプロファイルする.
- Ubl改変の異なる役割とネットワーク構造を調査する.
- Ublsの新たな機能,特に細胞周期調節における機能を特定する.
主な方法:
- 活性哺乳類の細胞抽出物を使った機能分析を用いた.
- 大規模な標的の識別のために使用されたタンパク質マイクロアレイ.
- ミトーシスとG1段階の間の改変プロファイルを比較した.
主要な成果:
- ユビキチンとUbls.のための約1,500の潜在的なタンパク質基板を特定しました.
- 個々のUbl.ごとに80〜200の固有のタンパク質標的を発見した.
- ほとんどのターゲットが単一のUbl.によって修正される非ランダムなネットワーク構造を明らかにしました.
- FAT10がミトス調節における重要な役割を強調した.
結論:
- 各Ublは,異なる分子機能を示し,特殊な生物学的な役割を示唆しています.
- この研究は,UBLの修正目標のための貴重なリソースを提供します.
- 細胞状態における翻訳後の改変を分析するための体系的なアプローチが確立されました.
- FAT10がミトーシスに果たす役割は,これまで考えられていたよりもはるかに重要だ.
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.
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...
Anaphase Promoting Complex
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
Regulation of Expression at Multiple Steps
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...
Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Histone Modification
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...


