Fas诱导的卡斯帕斯脱化
J B Mannick1, A Hausladen, L Liu
1Department of Adult Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA. joan_mannick@dfci.harvard.edu
概括
蛋白质S-化,是一种蛋白质的修饰,调节细胞信号传递. 这项研究表明,Fas通路的激活会使caspase-3化,增加其活性,并证明S-化在信号传导中的作用.
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:
- 蛋白质S-化在细胞信号传递中的作用在很大程度上仍未被探索.
- 迄今为止,很少有细胞内S-化蛋白被确定.
研究的目的:
- 调查蛋白质S-化和脱化是否参与信号传导通路.
- 通过S-基化检查caspase-3活动的调节.
主要方法:
- 在人类细胞系中分析caspase-3zymogens的S-nitrosylation状态.
- 研究Fas亡途径激活对caspase-3 S-nitrosylation的影响.
- 在caspase-3 S-nitrosylation与细胞内caspase活性相关的变化.
主要成果:
- 在未刺激的细胞中,发现卡斯帕-3细胞因子在它们的催化位点氨酸上被S-化.
- Fas通路的激活导致了caspase-3的脱化.
- 减少的caspase-3 S-nitrosylation与增加的细胞内caspase活性相关.
结论:
- 蛋白质S-化/脱化作为信号传导通路中的调节机制.
- Fas介导的亡包括caspase-3分裂和活性部位的醇脱化,以激活caspase-3.
相关概念视频
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...


