相关实验视频
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Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
Published on: June 29, 2011
Smac是一种线粒体蛋白质,通过消除IAP抑制来促进细胞染色体c-依赖的酶激活
1Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, 75235, USA.
Cell
|August 10, 2000
概括
一种新的线粒体蛋白质,Smac (第二线粒体衍生卡斯帕斯激活器),通过激活卡斯帕斯激活细胞,促进细胞亡. Smac 中和抑制蛋白质,增强编程细胞死亡信号通路.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 细胞亡,或编程细胞死亡,是一个关键的细胞过程.
- 酶激活是apoptotic执行的核心.
- 亡蛋白抑制剂 (IAP) 调节酶活动,防止细胞死亡.
研究的目的:
- 为了确定参与亡过程中酶激活的新型蛋白质.
- 阐明Smac影响亡途径的机制.
主要方法:
- 蛋白质的识别和表征.
- 蛋白质与蛋白质相互作用的分析.
- 细胞局部化研究.
- 评估Smac对酶激活和亡的作用.
主要成果:
- 识别Smac,一种新的线粒体蛋白质.
- 通过对抗IAPs,Smac促进了卡斯巴-9激活.
- 线粒体局部化和信号裂是Smac的亲细胞灭绝功能必不可少的.
- 过度表达Smac使细胞对亡刺激敏感.
结论:
- Smac是亡的关键媒介,作用于线粒体外膜透的下游.
- 在促进酶激活方面,Smac的功能类似于cytochrome c.
- 斯马克代表了调节亡的新目标.
相关概念视频
Translocation of Proteins into the Mitochondria
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Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
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...

