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， 由内在细胞生化程序执行的动物。发起 细胞凋亡通过细胞内信号和细胞间信号在动物体内发挥重要作用， 发育，维持正常组织稳态，消除 致瘤细胞和病毒感染细胞。癌症和自身免疫可能会出现， 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 神经变性疾病以及中风期间的神经元和心肌细胞死亡。 半胱天冬酶是一组进行细胞凋亡的细胞内蛋白酶。 半胱天冬酶是作为非活性酶原合成的，当细胞 致力于细胞凋亡。Caspase-3是一种主要的caspase， 负责产生许多特征性的生化和形态 凋亡的特征。其中一个主要的半胱天冬酶激活途径是 由线粒体通过释放凋亡蛋白酶激活 细胞色素c和Smac等因子。这些因素触发了 半胱天冬酶-3通过半胱天冬酶级联反应。 细胞色素c启动的caspase-3激活途径受到负调控 IAP是另一个结合并抑制caspase活性的蛋白质家族。 Smac中和IAP活性，并确保细胞凋亡时进行， 损坏得无法修复 该笔拨款建议继续进行胱天蛋白酶-3的生化研究， 激活过程，重点是IAP和Smac的调节。结果 产生的应该提供机制的见解，如何细胞的敏感性， 确定某种凋亡刺激。这样的知识应该提供 人类常见疾病诊断和治疗指南 以上

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.