Acinusは,アポプトティッククロマチン凝縮に必要なカスパース-3活性化タンパク質です
1Department of Medical Genetics, Biomedical Research Center, Osaka University Medical School, Suita, Japan.
Nature
|September 18, 1999
まとめ
研究者らは,アポプトティッククロマチンの凝縮に不可欠な新しい核因子Acinusを特定しました. カスパース3によって活性化されるこの因子は,DNAの断片化を引き起こすことなく,核の変化を誘導し,プログラムされた細胞死における特定の役割を強調する.
科学分野:
- 細胞生物学 細胞生物学
- 分子生物学は分子生物学である.
- バイオケミストリー バイオケミストリー
背景:
- アポプトシスは,クロマチンの凝縮と断片化のような明確な核形態学的変化を伴う.
- カスパース活性化により,これらのアポプトシス現象が始まり,カスパース活性化DNase (CAD/DFF40) とカスパース-6が関与します.
- CAD/DFF40は,精製された核でクロマチンの凝縮を誘導しますが,他の要因も関与している可能性があります.
研究 の 目的:
- アポプトティッククロマチンの凝縮に起因する新しい核因子を特定する.
- アポトーシス中の核形態学的変化におけるカスパース活性化因子の特定の役割を解明する.
主な方法:
- 核要因を隔離し,特定するために in vitro システムを活用しました.
- 特定された要因の必要性を評価するために,免疫低下実験を採用しました.
- この因子の役割をin vivoで検証するために,細胞でアンチセンセスの研究を行いました.
主要な成果:
- 新しい核因子,Acinusを特定し,カスパース-3分裂時にアポプトティッククロマチンの凝縮を誘導した.
- Acinus誘発の凝縮は,DNAの断片化とは独立して発生することを実証した.
- 免疫減退は,Acinusがアポプトティッククロマチンの凝縮を in vitro で果たす重要な役割を確認した.
- アンチセンセスの研究は,細胞のアポプトティッククロマチン凝縮におけるAcinusの重要性を確認した.
結論:
- Acinusは,アポプトティッククロマチンの凝縮に不可欠な新しいカスパース-3活性化核因子です.
- Acinusは,DNAの断片化とは異なるアポトーシス中の核形態学的変化を駆動する特定の役割を果たします.
- この発見は,プログラムされた細胞死を調節する分子機構の理解を広げています.
関連する概念動画
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...


