Rae1-Nup98复合物通过抑制securin降解来防止动质
Karthik B Jeganathan1, Liviu Malureanu, Jan M van Deursen
1Department of Pediatric and Adolescent Medicine, Mayo College of Medicine, 200 First Street SW, Rochester, Minnesota 55905, USA.
Nature
|December 16, 2005
概括
Rae1和Nup98通过抑制securin降解来调节亚纳酶促进复合体 (APC). 这可以防止过早的染色体分离和形形成,保持基因组的稳定性.
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:
- 亚纳酶促进复合体 (APC) 通过降解关键的线粒调节体来控制细胞循环的进展.
- 适当调节APC活性对于防止染色体误分和形形成至关重要.
研究的目的:
- 调查核细胞质运输因子Rae1和Nup98在调节分离过程中的APC活性中的作用.
- 阐明Rae1和Nup98控制蛋白降解并保持基因组稳定性的机制.
主要方法:
- 鼠标模型具有Rae1和Nup98组合的平分不充分性.
- 分析染色体分离,阳性积分和蛋白质降解.
- 同免疫沉试验用于研究蛋白质复合体的形成.
主要成果:
- 结合Rae1和Nup98的哈普隆缺陷导致过早的姐妹染色体分离,无积分体,以及不及时的蛋白质降解.
- 在早期的线粒分裂中,Rae1和Nup98与APC(Cdh1) 形成复合体,抑制了securin的无化.
- 从APC中Rae1/Nup98的解离 ((Cdh1) 与securin降解和线粒细胞进展相关.
结论:
- Rae1和Nup98作为APC的时间调节者,防止过早的securin降解.
- 这些因素对于通过确保及时和准确的染色体分离来维持euploidy至关重要.
相关概念视频
Nondisjunction
During meiosis, chromosomes occasionally separate improperly. This occurs due to failure of homologous chromosome separation during meiosis I or failed sister chromatid separation during meiosis II. In some species, notably plants, nondisjunction can result in an organism with an entire additional set of chromosomes, which is called polyploidy. In humans, nondisjunction can occur during male or female gametogenesis and the resulting gametes possess one too many or one too few chromosomes.
Separation 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...
The Spindle Assembly Checkpoint
The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
Anaphase Promoting Complex
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
Anaphase Promoting Complex
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
Nondisjunction
Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate correctly and move to the opposite poles of the cells. This produces daughter cells with abnormal chromosome numbers. Nondisjunction is common during anaphase I or anaphase II of meiosis. Mutations in synaptonemal complex proteins that attach homologous chromosomes increase the chances of nondisjunction in anaphase I of meiosis I. In contrast, mutations in topoisomerases and condensins that hold sister...


