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Analysis of Cell Cycle Position in Mammalian Cells
Published on: January 21, 2012
哺乳动物细胞在没有D型环林依赖激酶Cdk4和Cdk6的情况下循环
Marcos Malumbres1, Rocío Sotillo, David Santamaría
1Molecular Oncology Program, Centro Nacional de Investigaciones Oncológicas (CNIO), E-28029 Madrid, Spain. malumbres@cnio.es
Cell
|August 19, 2004
概括
循环素依赖性激酶4和6 (Cdk4/Cdk6) 不是细胞循环启动的必要条件. 替代途径可以驱动细胞增殖,以响应基信号,挑战以前的假设.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 发展生物学 发展生物学
背景情况:
- 循环素依赖性激酶4和6 (Cdk4/Cdk6) 传统上被认为对细胞循环启动至关重要.
- 之前的研究表明,Cdk4是不可用的,而Cdk6可能会补偿.
- Cdk6-null小鼠是可行的,但显示轻微的造血缺陷.
研究的目的:
- 调查Cdk4和Cdk6在细胞周期启动和增殖中的重要作用.
- 探索D型循环林依赖激酶在线虫发生反应中的补偿作用和必要性.
主要方法:
- 分析Cdk4/Cdk6缺乏的小鼠模型 (零和双零胚胎).
- 在体外增殖试验中,使用缺乏Cdk4和Cdk6的胚胎纤维细胞进行了试验.
- 在血清刺激后,评估静止细胞的细胞循环进入动力学.
主要成果:
- 缺少Cdk4和Cdk6的胚胎由于严重贫血而表现出胚胎致死性,但显示出正常的器官生成和细胞增殖.
- Cdk4/Cdk6-无胚胎纤维细胞在体外繁殖并成为不朽的.
- 静止的Cdk4/Cdk6-null细胞在刺激后进入S相,动力学正常,但效率降低.
结论:
- D型环素依赖激酶 (Cdk4/Cdk6) 对于启动细胞循环进入并非必不可少.
- 存在替代机制,以启动细胞增殖,以应对菌原性刺激.
- 这些发现需要重新评估Cdk4/Cdk6在细胞周期控制中的作用.
相关概念视频
Positive Regulator Molecules
To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
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.
Inhibition 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...
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...
Inhibition 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...
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...

