波罗酶通过向一个协激活蛋白来控制细胞循环依赖的转录
Zoulfia Darieva1, Richard Bulmer, Aline Pic-Taylor
1Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.
Nature
|November 24, 2006
概括
波罗基因酶Cdc5p控制细胞循环依赖的基因表达,这对线粒分裂至关重要. 通过Cdc5p对Ndd1p的酸化确保了像CLB2这样的关键线粒调节者的适当表达.
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:
- 波罗基纳斯对于真核细胞细胞循环调节在分裂过程中至关重要.
- 控制关键调节者的基因表达对于细胞周期进展至关重要.
- 模型真核生物Saccharomyces cerevisiae被用来研究保存的细胞循环机制.
研究的目的:
- 研究波罗基因酶Cdc5p在细胞循环依赖基因表达中的作用.
- 阐明Cdc5p调节线粒基因表达的机制.
- 为了确定Cdc5p介导调节对细胞分裂的影响.
主要方法:
- 研究了Cdc5p对基因促进体的时间招募.
- 通过Cdc5p分析了Ndd1p蛋白的酸化.
- 评估了野生型和突变菌株中细胞周期调节基因 (例如,CLB2,SWI5) 的表达.
- 在没有Cdc5p功能的情况下观察到细胞分裂表型.
主要成果:
- 在特定的细胞周期阶段,Cdc5p被招募到CLB2基因群的促进者中.
- 在Mcm1p-Fkh2p-Ndd1p复合体内,Cdc5p直接化Ndd1p联合激活剂.
- 这种酸化对于G2/M阶段基因的正确时间表达至关重要,包括CLB2和SWI5.5.
- 失去Cdc5p介导的Ndd1p酸化导致显著的细胞分裂缺陷.
结论:
- Cdc5p在调节细胞循环依赖的基因表达中发挥着关键作用,这对于线粒分裂是必需的.
- 通过Cdc5p对Ndd1p的酸化是产生必要的线粒调节者的关键机制.
- 波罗激酶活性对于线粒体事件编排和调节蛋白质的产生都是必要的,扩大其已知的功能.
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.
01:23Negative Regulator Molecules
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
02:36DNA Damage can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
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.
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...
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...