DFF是一种异构蛋白质,它在caspase-3的下游起作用,在亡过程中触发DNA碎片化
1Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Cell
|April 18, 1997
概括
研究人员在HeLa细胞中发现了一种DNA碎片化因子 (DFF). 通过caspase-3激活,DFF直接触发DNA碎片化,这是亡的一个关键事件.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 细胞亡是编程细胞死亡的关键过程.
- DNA碎片化是亡的一个标志.
- 启动DNA碎片化的分子机制尚未完全理解.
研究的目的:
- 为了识别和描述参与DNA碎片化的蛋白质在亡过程中.
- 阐明caspase-3在激活DNA碎片化的作用.
主要方法:
- 从HeLa细胞细胞质中净化蛋白质.
- 生物化学测试以评估DNA碎片化的情况.
- 蛋白质子单元和cDNA测序的分析.
主要成果:
- 一种新型的蛋白质DNA碎片化因子 (DFF) 被识别和净化.
- DFF是一种由40 kDa和45 kDa子单元组成的异构体.
- 卡斯帕酶-3的激活会分裂DFF的45kDa子单元,产生一个活跃的DNA分裂因子.
- 这种切割模式在体外镜像中反映了在亡细胞中观察到的情况.
结论:
- DFF是卡斯帕酶-3在亡途径中的直接下游标.
- 酶-3/DFF通路是亡过程中DNA碎片化的关键调解者.
- 这项研究揭示了直接信号传导级联导致DNA碎片化在亡.
相关概念视频
DNA 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...
Anaphase 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...
Apoptosis
Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
Caspases
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
The Extrinsic Apoptotic Pathway
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
The Intrinsic Apoptotic Pathway
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...


