Cdk1足以驱动哺乳动物细胞周期
David Santamaría1, Cédric Barrière, Antonio Cerqueira
1Molecular Oncology Programme, Centro Nacional de Investigaciones Oncológicas, E-28029 Madrid, Spain.
Nature
|August 19, 2007
概括
循环素依赖性激酶1 (Cdk1) 是哺乳动物中唯一重要的细胞循环激酶. 即使没有其他相间Cdks,Cdk1也会驱动细胞分裂,证明它在细胞增殖中的关键作用.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 哺乳动物的细胞分裂通常涉及多个循环素依赖激酶 (Cdks) 进行介相和分裂.
- 之前的研究表明,相间Cdk (Cdk2,Cdk3,Cdk4,Cdk6) 和它们的调节器之间存在冗余.
研究的目的:
- 调查介相Cdks在哺乳动物细胞周期进展中的重要性.
- 确定Cdk1在没有其他Cdk的情况下所扮演的角色.
主要方法:
- 产生缺乏所有相间Cdks (Cdk2,Cdk3,Cdk4,Cdk6) 的小鼠模型.
- 胚胎发育,器官发生和细胞增殖的分析.
- 对视网膜母细胞瘤蛋白 (pRb) 酸化和E2F向基因表达的评估.
- 培养和表征小鼠胚胎纤维细胞 (MEFs).
主要成果:
- 缺少所有相间Cdk的小鼠发展到中期,表明Cdk1弥补了它们的缺失.
- 在这些胚胎中,Cdk1与所有环林结合,酸化pRb,并激活了这些胚胎中的E2F调节基因.
- 来自这些胚胎的MEF在体外增殖,细胞周期延长,但成为不朽的.
- 缺少Cdk1的胚胎无法超越毛囊/母细胞囊阶段的发育.
结论:
- Cdk1是哺乳动物中唯一重要的细胞周期Cdk.
- 在没有相间Cdks的情况下,Cdk1可以执行所有必要的细胞分裂事件.
- 在早期胚胎发育中,Cdk1是必不可少的.
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相关概念视频
01:45Positive Regulator Molecules
To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
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.
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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...
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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...
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.
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