通过人类WEE1氨酸激酶对p34cdc2-cyclin B复合物的失活
1Department of Physiology, Tufts University School of Medicine, Boston, MA 02111.
Science (New York, N.Y.)
|September 25, 1992
概括
人类WEE1基因产物,氨酸激酶,使p34cdc2-环素B复合体失活,调节了线粒分裂的进入. 人类Cdc25C通过去酸化p34cdc2.2.来逆转这种抑制.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 在Schizosaccharomyces pombe中,线粒分裂的进入受 wee1+ 基因的调节.
- 微1+基因产物在氨酸15上酸化p34cdc2,使p34cdc2-环素B复合体失活.
研究的目的:
- 研究 wee1+基因 (WEE1Hu) 的人类同类的功能.
- 为了确定WEE1Hu是否直接调节人体细胞中的p34cdc2-环林B复合体.
主要方法:
- 细菌中WEE1Hu的过度产生.
- 在体外激酶试验中,使用纯化的人类WEE1激酶和p34cdc2-cyclin B复合物进行了激酶试验.
- 对人类Cdc25C蛋白活性进行检测.
主要成果:
- 人类WEE1激酶是氨酸特异性的.
- 在氨酸15上,WEE1Hu酸化p34cdc2,但不氨酸14,使p34cdc2-环林B复合体失活.
- 人类Cdc25C脱酸盐p34cdc2,逆转WEE1介导的抑制.
结论:
- 在人类细胞中,WEE1Hu直接调节p34cdc2-cyclin B复合体.
- 与WEE1Hu不同的一种激酶在氨酸14上酸化p34cdc2.
相关概念视频
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...
02:17Separation of Sister Chromatids
At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...
At the onset of anaphase, separase, a proteolytic enzyme, is...
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...
02:36DNA Damage Can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...