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Updated: Aug 7, 2026

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Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
Published on: June 29, 2011
細胞毒性T細胞由来グラン酵素BによるアポプトシスプロテアゼCPP32の活性化
A J Darmon1, D W Nicholson, R C Bleackley
1Department of Biochemistry, University of Alberta, Edmonton, Canada.
Nature
|October 5, 1995
まとめ
細胞毒性Tリンパ球は,CPP32.3を活性化するグラン酵素Bを用いて標的細胞を殺害する. このプロテアゼはアポトーシスを開始し,細胞媒介免疫とプログラム細胞死における重要なステップを明らかにします.
科学分野:
- 免疫学 免疫学とは
- 細胞生物学 細胞生物学
- 分子生物学は分子生物学である.
背景:
- 細胞毒性Tリンパ球 (CTL) 媒介の細胞毒性は,ウイルス感染症,腫瘍,自己免疫疾患に対する防御に不可欠です.
- CTLは,分泌された花粉酵素を通して標的細胞のアポトシスを誘発しますが,正確なメカニズムは不明です.
- グラン酵素Bはアポトーシスの誘発に不可欠ですが,直接の基板と活性化経路は不明です.
研究 の 目的:
- グラン酵素Bの細胞内基質を特定する.
- CTL媒介によるアポトーシスの分子メカニズムを解明する.
- プログラム細胞死におけるグラン酵素Bの役割を理解する.
主な方法:
- グラン酵素Bの活性を分析するインビトロアッセイ.
- プロテアゼの割れ分測定法について.
- タンパク質の活性化を検出するためのウェスタン・ブロッティング.
主要な成果:
- グラン酵素Bは,重要なプロテアゼ前駆体であるCPP32を直接割って活性化します.
- 活性化されたCPP32は,ポリアドプリボゼ) ポリメラーゼ (PARP) の分裂に責任があります.
- この分裂カスケードは,標的細胞におけるDNA断片化とアポトーシスの開始に不可欠です.
結論:
- グラン酵素Bは,アポプトシス経路における重要な処刑タンパク質であるCPP32を活性化します.
- グラン酵素B-CPP32-PARP軸は,CTL誘発細胞死における中心的なメカニズムを表しています.
- この経路を理解することは,免疫反応を調節し,CTLを伴う疾患の治療に不可欠です.
関連する概念動画
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.
Cellular Injury V: Apoptosis and Autophagy
Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...

