SCFFbw7ユビキチンリガゼによるサイクリンEのリン酸化依存型ユビキチン化
D M Koepp1, L K Schaefer, X Ye
1Department of Biochemistry and Molecular Biology, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX, 77030, USA.
まとめ
この研究では,SCFFbw7を,サイクリンEタンパク質のレベルを制御するユビキチンリガゼとして特定しています. このメカニズムは種ごとに保たれ,適切な細胞サイクル進行を保証する.
科学分野:
- 細胞生物学 細胞生物学
- 分子生物学は分子生物学である.
- バイオケミストリー バイオケミストリー
背景:
- サイクリンE/Cdk2複合体は,G1からS段階への移行を駆動する.
- サイクリンEタンパク質の濃度の厳格な調節は,細胞サイクル制御に極めて重要です.
- ウビキチン媒介タンパク質分解は,タンパク質分解の重要なメカニズムである.
研究 の 目的:
- サイクリンEのユビキチン化に責任を負うユビキチンリガゼを特定する.
- このリガースの機能的保存を異なる種で調査する.
- サイクリンEタンパク質の安定性と細胞周期調節におけるSCFFbw7の役割を理解する.
主な方法:
- 生物化学的分析により,ユビキチンリガゼの識別.
- SCFFbw7とCyclin E.を使用したインビトロユビキチネーションアッセイ.
- 人体,ハエ,酵母細胞の遺伝子枯渇を含むインビボ研究.
- タンパク質の蓄積と安定性の分析.
主要な成果:
- SCFFbw7は,サイクリンEの特定のユビキチンリガゼとして特定されました.
- Fbw7は特に,リン酸化サイクリンEと関連している.
- SCFFbw7は,サイクリンEのユビキチン化をインビトロで触媒化する.
- Fbw7の枯渇は,サイクリンEの蓄積とin vivoの安定化につながります.
- 酵母,ハエ,哺乳類で実証されたサイクリンEの安定性を調節するFbw7の機能的保存.
結論:
- SCFFbw7は,E3ウビキチンリガゼで,サイクリンEを分解する主な標的である.
- サイクリンEのFbw7媒介の分解経路は,進化的に保存されています.
- SCF E3リガゼによるサイクリンE安定性の組み合わせ制御は,酵母における発見によって示唆されています.
関連する概念動画
Positive Regulator Molecules
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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...
Positive Regulator Molecules
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
Separation of Sister Chromatids
At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
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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...
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...


