将p35转换为p25可以调节Cdk5的活性,并促进神经退行
G N Patrick1, L Zukerberg, M Nikolic
1Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature
|December 22, 1999
概括
一种截断的蛋白质,p25,积聚在阿尔茨海默病的大脑中,增加了Cdk5的活动. 这导致陶过酸化,细胞骨损伤和神经元死亡,这表明它在神经退行症中起作用.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 循环素依赖性激酶5 (Cdk5) 对于哺乳动物中枢神经系统的发育至关重要.
- Cdk5的激活需要与其调节子单元相关联,p35.
研究的目的:
- 为了研究一个截断的p35蛋白,p25在阿尔茨海默氏病的发病过程中的作用.
- 确定p25积累对Cdk5活动和神经元功能的影响.
主要方法:
- 来自阿尔茨海默病患者的大脑组织的分析.
- 生物化学试验测量Cdk5激酶活性.
- 细胞培养实验研究p25/Cdk5复合物的作用.
主要成果:
- p25在阿尔茨海默病大脑中的神经元中积累,与Cdk5活性增加相关.
- 结合p25与Cdk5导致构成性激活,改变细胞局部化和基质特异性.
- 在p25/Cdk5复合物中,酸盐过,使微管不稳定,并在体外诱导神经元退化和亡.
结论:
- 在阿尔茨海默病中,p35的裂变形成p25及其随后的积累可能导致细胞骨异常和神经元死亡.
- 异常的p25/Cdk5复合体与神经退行性疾病的发病有关.
相关概念视频
Negative 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.
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...
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...
Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
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...
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...


