Caspase Activation in Apoptosis

描述：(由申请者提供)程序性细胞死亡，或称细胞凋亡 在所有多细胞生物体的整个生命过程中都扮演着至关重要的角色。这 机制允许在发育过程中受控地移除细胞 雕塑身体，保持身体结构和组织大小，还 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 受调节的过程或其他各种异常和疾病可能由 细胞死亡不是太多就是太少。其中包括各种发展中的 缺陷、神经退行性疾病、自身免疫性疾病和癌症。中心到 这个过程是一个半胱氨酸蛋白酶家族，称为半胱氨酸酶。他们的 激活会导致典型的形态变化，在 细胞凋亡及其调控是适当控制细胞凋亡的关键。这个 这项提案的目标是提供结构框架，该框架将 使我们能够理解caspase被激活的机制 它们不活跃的酶原形成一种完全活跃的酶，以及它们如何与 酶活性，并最终影响细胞功能。我们将专注于 尤其是caspase-9的激活。

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.