p21是一种环林酶的通用抑制剂
1Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York 11724.
Nature
|December 16, 1993
概括
蛋白质p21作为循环素依赖激酶 (CDK) 的通用抑制剂,对调节细胞增殖至关重要. 它在转化细胞中的损失表明它在癌症发育和细胞周期控制中起着关键作用.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 在瘤学瘤学.
背景情况:
- 细胞增殖放松调控是瘤转变的一个关键特征.
- 改变的生长控制途径会影响细胞循环机制,但机制尚不清楚.
- 病毒瘤蛋白诱导转化细胞中循环素依赖激酶 (CDK) 复合体的变化.
研究的目的:
- 研究转化细胞CDK复合体中增殖细胞核抗原 (PCNA) 和p21损失的意义.
- 阐明p21在细胞循环调节中的作用.
- 在体外复制四级细胞循环激酶复合物.
主要方法:
- 对p21基因进行分子克隆.
- 在实验室中复制四级细胞循环激酶复合物.
- 测试以确定p21对环林/CDK活性和细胞增殖的影响.
主要成果:
- 克隆了p21并研究了它在细胞循环调节中的作用.
- 发现p21抑制了所有测试的cyclin/CDK家族成员的活性.
- 过度表达p21抑制了哺乳动物细胞中的增殖.
结论:
- p21作为环林酶的通用抑制剂.
- 转化细胞中CDK复合物的p21损失可能导致不受控制的增殖.
- p21是细胞循环的关键调节剂,在癌症治疗中是一个潜在的目标.
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.
02:39Positive 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...
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...
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...