Caspase Activation in Apoptosis

描述：（由申请人提供）程序性细胞死亡或凋亡， 在所有多细胞生物的生命中起着至关重要的作用。这 这种机制允许在发育过程中控制细胞的去除， 雕塑身体，保持身体结构和组织大小， 用于清除受损或受感染的细胞。细胞凋亡必须是一个紧密的 调节过程或其他各种异常和疾病可能会出现， 细胞死亡过多或过少其中包括各种发展 缺陷、神经变性疾病、自身免疫疾病和癌症。的核心 这个过程是半胱氨酸蛋白酶家族，称为半胱天冬酶。他们的 激活导致典型的形态学变化， 细胞凋亡，因此它们的调节是适当控制细胞凋亡的关键。的 本建议的目的是提供结构框架， 使我们能够理解半胱天冬酶被激活的机制， 它们的无活性的酶原形成完全活性的酶，以及这些如何与 酶活性并最终影响细胞功能。我们将重点 特别是半胱天冬酶-9激活。

DESCRIPTION: (provided by applicant) Programmed cell death, or apoptosis, plays a crucial role throughout the life of all multicellular organisms. This mechanism allows for the controlled removal of cells during development in sculpturing the body, maintaining body structure and tissue size, and is also used for eliminating damaged or infected cells. Apoptosis has to be a tightly regulated process or else various abnormalities and diseases may arise from either too much or too little cell death. These include various developmental defects, neurodegenerative diseases, autoimmune diseases and cancer. Central to this process are a family of cysteine proteases called caspases. Their activation leads to the typical morphological changes that occur during apoptosis and thus their regulation is key for proper control of apoptosis. The objectives of this proposal is to provide the structural framework which will enable us to understand the mechanism by which caspases are activated from their inactive, zymogen form to a fully active enzyme, and how these relate to enzymatic activity and ultimately to cellular function. We will focus specifically on caspase-9 activation.