通过无相促进复合体的乌比基因化驱动螺旋检查点不活化
S K Reddy1, M Rape, W A Margansky
1Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature
|April 20, 2007
概括
细胞检查点通过抑制亚纳相促进复合体 (APC) 来确保精确的染色体分离. 无活化涉及APC依赖的多重ubiquitination,释放抑制并允许细胞分裂.
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 遗传学 是一个
背景情况:
- 细胞利用螺旋检查点进行精确的染色体分离.
- 这个检查点防止姐妹染色体的分离,直到kinetochores实现双极旋附着.
- 检查点蛋白质抑制了亚纳酶促进复合体 (APC),这是一个在线分裂中至关重要的泛基因酶.
研究的目的:
- 阐明细胞从螺旋检查点抑制转换为快速激活的机制.
- 为了了解染色体分离是如何迅速启动后,kinetochore附着.
- 探索癌细胞中受损的螺旋检查点的潜在原因.
主要方法:
- 研究了在检查点不活化过程中,APC依赖多部位化的作用.
- 研究了检查点蛋白 (Mad2,BubR1) 与Cdc20的分离.
- 鉴定出一种去无化酶,可以逆转Cdc20的无化.
主要成果:
- 螺旋检查点无活化是一个能源依赖的过程,涉及APC介导的多元无处置.
- 多重ubiquitination导致Mad2和BubR1从Cdc20脱离,从而使APC激活.
- 一种除ubiquitin化酶逆转了这个过程,突出了调节周期.
结论:
- 检查点蛋白和APC之间的相互作用确保了及时的染色体分离.
- 这种机制使细胞能够迅速激活APC,一旦kinetochore附着完成.
- 这些发现为了解没有直接突变的癌症中螺旋检查点缺陷提供了基础.
相关概念视频
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01:39Anaphase A and B
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00:50Anaphase Promoting Complex
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02:19The 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...
00:50Anaphase 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...