对Cdk1基质化位点的全球分析为进化进化提供了洞察力
Liam J Holt1, Brian B Tuch, Judit Villén
1Departments of Physiology and Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
概括
研究了细胞周期控制机制,通过分析酵母中的循环素依赖激酶Cdk1酸化位. 大多数地点都没有保存,转移到无序的区域,这表明激酶信号电路的快速演变.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 进化生物学 进化生物学
背景情况:
- 细胞循环控制对细胞功能和生物体发育至关重要.
- 循环素依赖激酶 (CDKs) 在调节细胞循环方面发挥着至关重要的作用.
- 了解CDK调节的演变,可以深入了解细胞复杂性.
研究的目的:
- 调查CDK酸化场所的进化保存和位置动态.
- 探索酸化调节蛋白质功能和相互作用的机制.
- 了解酶信号网络的演变.
主要方法:
- 使用定量质谱法在体内确定CDK酸化位.
- 用Cdk1的特定化学抑制来绘制其基质.
- 在ascomycete血统中对CDK基质进行了比较基因组分析.
主要成果:
- 在Saccharomyces cerevisiae中,在308个Cdk1基板上确定了547个酸化位.
- 大多数酸化位点的位置在进化过程中并未得到保存.
- 酸化位点在快速演变的无序蛋白质区域内聚集和转移.
结论:
- 酸化介导的蛋白质功能调节通常依赖于简单的,非特异性的蛋白质-蛋白质相互作用的破坏或增强.
- 在动态区域中酸化位点的增加或损失可以推动激酶信号通路的演变.
- 这项研究为了解细胞循环调节通过转化后修改的演变提供了一个框架.
相关概念视频
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.
Positive Regulator Molecules
To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
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...
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...
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...


