ミトーシスの発生時に空間的なポジティブなフィードバック
Silvia D M Santos1, Roy Wollman, Tobias Meyer
1Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305-5174, USA. sdsantos@stanford.edu
Cell
|June 26, 2012
まとめ
核Cdk1-サイクリンB1は,独自の核転位を促進し,空間的なポジティブなフィードバックループを作成します. これにより,細胞循環の調節に不可欠なミトーシスへの迅速かつ不可逆的な入り口が確保されます.
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:
- ミトーシスの開始は,Cdk1-サイクリンB1の活性化と核転位に依存しています.
- プラスのフィードバックループは,Cdk1-サイクリンB1の活性化を調節し,不可逆的なオール・オア・ノー応答を保証することが知られている.
- Cdk1-サイクリンB1の再分配の調節における空間的ポジティブフィードバックの役割は不明のままである.
研究 の 目的:
- 空間的な陽性フィードバックがCdk1-サイクリンB1.1の転位を調節するかどうかを調査する.
- この空間的フィードバックループの背後にあるメカニズムを解明する.
- ミトーシスのCdk1-サイクリンB1転位ダイナミクスの機能的意義を決定する.
主な方法:
- 化学生物学のアプローチを活用した.
- 生細胞顕微鏡を用いた.
- リン酸化と転移の関係を探求するためのメカニズム研究を行いました.
主要な成果:
- 核Cdk1-サイクリンB1が核への自身の転位を促進することを実証しました.
- サイクリンB1のリン酸化が核転位を促進し,その逆の相互関係が特定されました.
- トランスロケーションの急激さを妨害すると,ミトスのタイミングとシンクロニーに影響を及ぼすことが示されました.
結論:
- 空間的なポジティブなフィードバックのモデルを提案し,迅速で,完全で,堅牢で,不可逆的なミトーシスへの入り口を確保した.
- ビスタブルな時空スイッチが生物学における一般的な規制メカニズムである可能性を示唆した.
- ミトスの進行に対する,規制されたCdk1-サイクリンB1転位の機能的重要性を強調した.
関連する概念動画
Forces Acting on Chromosomes
During mitosis, chromosome movements occur through the interplay of multiple piconewton level forces. In prometaphase, these forces help in chromosome assembly or congression at the equatorial plane, eventually leading to their alignment at the metaphase plate. The forces acting on the chromosomes are space and time-dependent; therefore, they vary with the position of the chromosomes as the cell progresses through mitosis.
Microtubules and motor proteins exert two types of forces on...
Microtubules and motor proteins exert two types of forces on...
Forces Acting on Chromosomes
During mitosis, chromosome movements occur through the interplay of multiple piconewton level forces. In prometaphase, these forces help in chromosome assembly or congression at the equatorial plane, eventually leading to their alignment at the metaphase plate. The forces acting on the chromosomes are space and time-dependent; therefore, they vary with the position of the chromosomes as the cell progresses through mitosis.
Microtubules and motor proteins exert two types of forces on...
Microtubules and motor proteins exert two types of forces on...
M-Cdk Drives Transition Into Mitosis
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
M-Cdk Drives Transition Into Mitosis
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Attachment of Sister Chromatids
As cells progress into mitosis, the nuclear envelope breaks down, and the condensed chromosomes are exposed to the array of bipolar microtubules of the mitotic spindle. The kinetochore, a large, disc-shaped protein complex, is present at the centromere region of the sister chromatids and acts as a binding site for the microtubules. Usually, the plus-end of a single microtubule is embedded within the kinetochore. However, some kinetochores first establish lateral contact with the side-wall of a...
The Mitotic Spindle
The mitotic spindle—or spindle apparatus—is a eukaryotic, cytoskeletal structure made up of long protein fibers called microtubules. Formed during cell division, the spindle separates sister chromatids and moves them to opposite ends of a parental cell, where the now individual chromosomes are distributed to two daughter cell nuclei.
The bipolar configuration of the mitotic spindle facilitates chromosomal segregation, preparing the cell for division. One mechanism that ensures bipolar mitotic...
The bipolar configuration of the mitotic spindle facilitates chromosomal segregation, preparing the cell for division. One mechanism that ensures bipolar mitotic...


