Acinus 是一个 caspase-3 激活的蛋白质,需要用于 apoptotic 染色质凝聚
1Department of Medical Genetics, Biomedical Research Center, Osaka University Medical School, Suita, Japan.
Nature
|September 18, 1999
概括
研究人员发现了一种新的核因子,Acinus,对缩性染色体凝聚至关重要. 这种因子由酶-3激活,驱动核变化而不会导致DNA碎片化,突出其在编程细胞死亡中的特定作用.
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:
- 亡包括明显的核形态变化,如染色质的凝聚和碎片化.
- 酶激活启动了这些亡事件,其中酶激活的DNase (CAD/DFF40) 和酶-6都涉及.
- 虽然CAD/DFF40在净化核中诱导染色质凝聚,但可能还有其他因素参与其中.
研究的目的:
- 为了确定新型核因子,负责apoptotic染色体凝聚.
- 阐明酶激活因子在核亡过程中的核形态变化中的特定作用.
主要方法:
- 利用一个体外系统来隔离和识别核因素.
- 采用免疫减弱实验来评估确定因素的必要性.
- 在细胞中进行了反意义研究,以验证因子在生物体中的作用.
主要成果:
- 确定了一种新的核因子,Acinus,它在caspase-3裂变时诱导了apoptotic染色体凝聚.
- 证明Acinus诱导的凝结发生在DNA碎片化独立的过程中.
- 免疫缺陷证实了Acinus在体外光性染色体凝聚中的重要作用.
- 反意义研究证实了Acinus在细胞亡性染色体凝聚中的重要性.
结论:
- Acinus 是一种新型的 caspase-3 激活核因子,对缩性染色体凝聚至关重要.
- 在核细胞灭绝过程中,Acinus在驱动核形态变化的过程中发挥着特定的作用,这与DNA碎片化不同.
- 这一发现扩大了对调节编程细胞死亡的分子机制的理解.
相关概念视频
Condensins
Condensins are large protein complexes that use ATP to fuel the assembly of chromosomes during mitosis. They transform the tangled, shapeless mass of post-interphase DNA into individualized chromosomes by compacting, organizing, and segregating chromosomal DNA.
The plant and animal cells contain two types of condensin complexes—condensin I and condensin II. Both complexes have five subunits: two SMC (Structural Maintenance of Chromosomes) subunits, a kleisin subunit, and two HEAT-repeat...
The plant and animal cells contain two types of condensin complexes—condensin I and condensin II. Both complexes have five subunits: two SMC (Structural Maintenance of Chromosomes) subunits, a kleisin subunit, and two HEAT-repeat...
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...


