TFIIH是由含有cdk8的媒介体复合体负调节的
S Akoulitchev1, S Chuikov, D Reinberg
1Howard Hughes Medical Institute, Department of Biochemistry, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
Nature
|September 19, 2000
概括
循环素依赖酶8 (cdk8) 通过酸化循环素H来调节转录,影响转录因子TFIIH. 这一发现将调解者复合体与更高生物体的基底转录机制联系起来.
科学领域:
- 分子生物学分子生物学
- 基因法规 基因法规
- 生物化学 生物化学
背景情况:
- 循环素依赖酶8 (cdk8) 与急性淋巴细胞白血病和转录调节有关.
- 哺乳动物cdk8/cyclin C和酵母Srb10/Srb11是RNA聚合酶II全酶的一部分,作为激酶起作用.
- 在抑制转录的调解者类复合体中发现了cdk8/cyclin C复合体.
研究的目的:
- 研究cdk8/cyclin C在转录上的调节机制.
- 确定cdk8/cyclin C如何与一般转录启动因子IIH (TFIIH) 相互作用.
主要方法:
- 研究了通过cdk8.8对哺乳动物环林H的酸化.
- 在体外评估了这种酸化对TFIIH活性的影响.
- 研究了模仿cdk8酸化对循环林H的体内效应.
主要成果:
- Cdk8在其独特的螺旋域附近化哺乳动物环林H.
- 这种酸化抑制了TFIIH的转录激活和CTD激酶活性.
- 在体内模仿cyclin H的cdk8酸化对细胞生长产生了主导负效应.
结论:
- Cdk8/cyclin C通过准TFIIH子单元来调节转录.
- 涉及cdk8和TFIIH的监管途径连接了调解器复合体和基底转录机制.
- 这种调节途径似乎是高层生物的特征.
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...
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...