アナフェーズ促進複合カップルのミトーシスの自律的調節からS相への入り口まで
Michael Rape1, Marc W Kirschner
1Department of Systems Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA.
Nature
|November 24, 2004
まとめ
アナフェーズ促進複合体 (APC) は,サイクリンを分解することによって,細胞サイクル進行を制御する. この研究は,APCの活性がG1段階においてどのように下調され,サイクリンAの蓄積と細胞サイクル移行を可能にするかを明らかにしています.
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:
- サイクリン依存キナーゼ (CDK) 活性振動が体細胞サイクルを駆動する.
- アナフェーズ促進複合体 (APC) は,サイクリン分解を促進することによって,ミトーシスとミトーシス脱出を調節する.
- APCを無効化しS相を開始するサイクリンA再蓄積のメカニズムは不明のままである.
研究 の 目的:
- 活性APCにもかかわらず,G1期間にサイクリンAが蓄積するメカニズムを解明する.
- APCの活性が,細胞サイクル進行を可能にするために,どのように自律的に調節されるかを理解する.
主な方法:
- G1段階のAPC規制におけるUbcH10の役割を調査しました.
- APCの基板相互作用と自己活化を研究するために生化学的測定を用いた.
- UbcH10の分解がAPC活動とサイクリンAレベルに与える影響を分析した.
主要な成果:
- APCはG1の間にサイクリンAの蓄積を許容する状態に自律的に移行します.
- UbcH10の APC ((Cdh1) 依存的な分解は,この移行に不可欠です.
- APC基板はUbcH10のオートウビキチン化を阻害し,G1基板が枯渇するまでAPCの活性を維持する.
- UbcH10の分解は,サイクリンAの安定化とAPCのダウンレギュレーションにつながります.
結論:
- 細胞サイクルは,CDKとAPCの活動を交互に駆動する調節された振動器として動作します.
- APCは,UbcH10の分解によって自律的に自身の活動をダウンレギュレーションし,細胞サイクル進行を促進します.
- このメカニズムは,細胞周期の適切なタイミングを保証し,S相への早期のエントリーを防止します.
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00:50Anaphase Promoting Complex
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02:17Separation 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.
At the onset of anaphase, separase, a proteolytic enzyme, is...
At the onset of anaphase, separase, a proteolytic enzyme, is...
02:19The Spindle Assembly Checkpoint
The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
00:50Anaphase 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...