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Analysis of Cell Cycle Position in Mammalian Cells
Published on: January 21, 2012
细胞循环调节的c-Abl氨酸激酶与DNA的结合
1Department of Biology, University of California San Diego, La Jolla 92093-0116.
Science (New York, N.Y.)
|April 17, 1992
概括
原型瘤基因c-Abl蛋白质氨酸激酶通过其碳素终端域结合DNA. 这种DNA结合对c-Abl功能至关重要,并且由于酸化而在线粒分裂过程中丢失.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 瘤发生的发生因子.
背景情况:
- 原型瘤基因c-Abl编码一种具有细胞质和核定位的蛋白质氨酸激酶.
- c-Abl在细胞过程中发挥作用,但其精确的功能,特别是核作用,需要进一步阐明.
- 了解c-Abl活动的调节对于理解其参与癌症发展至关重要.
研究的目的:
- 为了研究c-Abl蛋白氨酸激酶的DNA结合能力.
- 确定卡基终端域在c-Abl与染色素的关联中所起的作用.
- 探索细胞周期期间c-AblDNA结合活动的调节,特别是细胞分裂.
主要方法:
- 生物化学测试以确定c-Abl蛋白中的DNA结合域.
- 染色体关联研究以证实c-Abl与DNA的相互作用.
- 使用cdc2激酶进行体外激酶试验,以研究酸化对DNA结合活性的影响.
- 对缺乏c-Abl DNA结合域的突变小鼠的分析.
主要成果:
- 在c-Abl的炭基末端段中,含有DNA结合域,这对于染色体协会至关重要.
- c-Abl的DNA结合活性在cdc2基因酶对carboxyl终端段的酸化后的线粒分裂期间被废除.
- 缺少c-Abl DNA结合域的同卵性突变小鼠在出生时表现出致命的发育缺陷.
结论:
- c-Abl的DNA结合域对其生物功能至关重要.
- 调控c-AblDNA结合的调节,通过线粒分裂期间的酸化,是控制其活动的关键机制.
- c-Abl与DNA的相互作用对于正常发育和生存至关重要.
相关概念视频
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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...