一种ICE类蛋白酶在Fas介导的亡过程中的参与
Nature
|May 4, 1995
概括
这项研究揭示了一种类似于interleukin-1β转化酶 (ICE) 的蛋白酶在Fas介导的细胞亡和瘤亡因子 (TNF) 细胞毒性中起着至关重要的作用. 抑制这种蛋白酶阻断细胞死亡,突出其在这些细胞过程中的重要性.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- Fas是一种I型膜蛋白,在结合Fas连接体或agonistic抗Fas抗体后启动细胞亡.
- 在Caenorhabditis elegans中进行的研究表明,诸如介素-1β转化酶 (ICE) 和ceded-3之类的蛋白酶参与了亡信号传递.
- 牛病毒编码的细胞因子反应修饰剂A (crmA) 抑制ICE活动.
研究的目的:
- 研究ICE类蛋白酶在Fas介导的亡和TNF诱导的细胞毒性中的作用.
- 确定抑制ICE类蛋白酶是否可以防止由抗Fas抗体或TNF诱导的细胞死亡.
主要方法:
- 在细胞中表达crmA,一种ICE抑制剂.
- 用抗法斯抗体或瘤亡因子 (TNF) 治疗.
- 使用一种特定的ICE抑制剂四甲 (乙-泰尔-瓦尔-阿拉-阿斯普-甲基).
主要成果:
- 表达crmA抑制的细胞毒性,由抗Fas抗体和TNF.诱导.
- 特定的ICE抑制剂四烯也防止了由抗Fas抗体诱导的亡.
- 这些发现表明ICE类蛋白酶在这些细胞死亡途径中起着关键作用.
结论:
- 一种类似于ICE的蛋白酶参与了Fas介导的亡.
- 类似ICE的蛋白酶与TNF诱导的细胞毒性有关.
- 准ICE类蛋白酶可能为控制亡和细胞毒性提供治疗策略.
相关概念视频
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...
Phagocytosis of Apoptotic Cells
Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or immature dendritic cells. Non-professional phagocytes such as epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes.
Normal cells contain receptors that prevent them from being recognized by phagocytes.
Normal cells contain receptors that prevent them from being recognized by phagocytes.
MAPK Signaling Cascades
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...


