雌激素受体的CDK独立激活由环林D1通过环林D1激活
R M Zwijsen1, E Wientjens, R Klompmaker
1Department of Tumor Biology, Netherlands Cancer Institute (Antoni van Leeuwenhoekhuis), Amsterdam.
Cell
|February 7, 1997
概括
环素D1增强雌激素受体 (ER) 活性和基因转录,独立于其CDK合作伙伴. 这种新的功能增强了乳腺细胞生长调节,即使没有雌激素.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 内分泌学 在内分泌学.
背景情况:
- 雌激素和cyclin D1是乳腺上皮细胞增殖的关键调节剂.
- 雌激素受体 (ER) 信号传递在对雌激素敏感组织的生长中起着关键作用.
研究的目的:
- 调查cyclin D1在对雌激素敏感组织的生长调节中的新型作用.
- 阐明cyclin D1影响雌激素受体介导基因转录的机制.
主要方法:
- 测试用于测量雌激素受体的转录活性.
- 同免疫沉检测循环素D1和ER之间的物理结合.
- 分析ER与雌激素反应元素 (ERE) 结合的ER.
主要成果:
- 环素D1强化了独立于CDK合作伙伴的ER介导转录.
- 环素D1在缺少和存在雌激素的情况下激活ER转录.
- 环素D1直接与ER激素结合域结合,增强受体与EREs的结合.
- 这种激活不会被抗雌激素阻断.
结论:
- 环素D1作为一种新型的,独立于CDK的雌激素受体激活剂.
- 环素D1与ER的相互作用增强了基因转录,影响了乳腺上皮细胞的生长调节.
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.
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...
02:15M-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...
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...
02:15M-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...