一个定量模型,用于Cdk基质在线性退出过程中的有序脱化
Céline Bouchoux1, Frank Uhlmann
1Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, London WC2A 3LY, UK.
Cell
|November 15, 2011
概括
线性退出涉及有序的事件. 在芽酵母中,不同的Cdk基质脱化时间显示了酸酶和激酶活动如何控制细胞周期进展.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 线粒体退出是在姐妹染色体分离之后发生的,并且涉及通过循环素依赖激酶 (Cdk) 脱化众多基质.
- 在线粒体退出期间,这些脱化事件的时间顺序的确切机制仍然不太清楚.
研究的目的:
- 为了研究Cdk基质脱化在发芽酵母中线性退出期间的有序时间.
- 阐明了在线粒体退出过程中建立事件时间序列的机制.
主要方法:
- 在体内实验调节循环林依赖激酶 (Cdk) 和Cdc14酸酶活动.
- 在Cdk基质酸化和脱酸化的体外运动分析.
- 测试不同的模型,以测试线粒体退出事件的时间顺序.
主要成果:
- 参与连续的线粒体退出事件的Cdk基质的脱化发生在有序的时间表上.
- 酸酶与酸酶的比率在线粒离子退出过程中逐渐发生变化.
- Cdk基板对这种比率变化的截然不同的值做出反应,导致有序脱.
结论:
- 酸酶与酸酶比率的逐渐转变提供了一种定量机制,可以对线粒体退出事件进行排序.
- 这项研究为细胞循环进展的定量模型提供了一种机制性的解释.
- 发芽酵母的发现提供了对基本细胞循环调节的见解.
相关概念视频
02:15M-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...
02:15M-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...
02:39Positive 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.
01:45Positive Regulator Molecules
To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
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...
02:34Inhibition of Cdk Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...