Biochemical characterization of caspase-3 activation

描述(由申请人提供)：细胞凋亡是细胞死亡的一种形式 由固有的细胞生化程序执行的动物。已启动 通过细胞内和细胞内信号，细胞凋亡在动物体内起着至关重要的作用 发展，维持正常组织的动态平衡，并消除 致瘤细胞和病毒感染细胞。癌症和自身免疫在以下情况下可能会发生 正常的细胞凋亡是有缺陷的，导致细胞数量过多。 相反，细胞凋亡可能在疾病中过早激活，包括 神经退行性疾病，以及中风期间神经元和心肌细胞的死亡。 半胱氨酸天冬氨酸氨基转移酶是一组执行细胞凋亡的细胞内蛋白水解酶。 半胱氨酸天冬氨酸氨基转移酶被合成为不活跃的酵素，当细胞 都致力于细胞凋亡。Caspase-3是一种主要的caspase 负责产生许多特征的生化和形态 细胞凋亡的特点。Caspase激活的主要途径之一是 线粒体通过释放凋亡酶激活而启动 细胞色素c、Smac等因子。这些因素触发了对 Caspase-3通过一系列caspase。 细胞色素c启动的caspase-3激活途径是负调控的 IAPs是另一个结合和抑制caspase活性的蛋白质家族。 Smac中和IAP活性，确保细胞在 损坏得无法修复。 这项拨款建议继续进行caspase-3的生物化学研究。 激活过程，重点是IAP和SMAC的监管。结果是 应该提供对细胞如何敏感性的机械见解 确定了一种特定的细胞凋亡刺激。这样的知识应该提供 列出的常见人类疾病的诊断和治疗指南 上面。

DESCRIPTION (provided by the applicant): Apoptosis is a form of cell death in animals that is executed by intrinsic cellular biochemical programs. Initiated by inter, and intracellular signals, apoptosis plays essential roles in animal development, maintaining normal tissue homeostasis, and elimination of tumorigenic and viral infected cells. Cancer and autoimmunity may arise when normal apoptosis is defective, resulting in excess numbers of cells. Conversely, apoptosis may be prematurely activated in diseases including neurodegenerative diseases, and neuron and cardiomyocyte death during stroke. Caspases are a group of intracellular proteases that carry out apoptosis. Caspases are synthesized as inactive zymogens that become activated when cells are committed to apoptosis. Caspase-3 is one of the major caspases that are responsible for generating many characteristic biochemical and morphological features of apoptosis. One of the major caspase activation pathways is initiated by mitochondria through the release of apoptotic protease activating factors such as cytochrome c and Smac. These factors trigger the activation of caspase-3 through a cascade of caspases. The cytochrome c-initiated caspase-3 activating pathway is negatively regulated by IAPs, another family of proteins that bind and inhibit caspase activities. Smac neutralizes IAP activity and ensure apoptosis to proceed when cells are damaged beyond repair. This grant proposes to continue the biochemical studies on the caspase-3 activating process focusing on the regulation by IAPs and Smac. The results generated should provide mechanistic insights into how a cell's sensitivity to a certain apoptotic stimulus is determined. Such knowledge should provide guidance to the diagnosis and therapy of the common human diseases listed above.