REGULATION OF APOPTOSIS BY ICH1S

程序性细胞死亡（或凋亡）对于细胞的生长和分化具有核心重要性。 发育、体内平衡，以及包括癌症在内的许多疾病， 获得性免疫缺陷综合征和神经变性疾病。 在遗传控制下，它是通过激活一个 由于内部或外部 信号. ICE/CED-3半胱氨酸蛋白酶家族自主地作为 死亡细胞中的效应子。Nedd-2/Ich-1是这个家族的一员， 鉴定出可以诱导组织培养细胞的凋亡。我 目前的工作表明ICH-1在凋亡过程中被激活。的 本提案的总体目标是， ICH-1在细胞凋亡中的作用及其激活机制。 具体 目的包括：i）检测原发组织中ICH-1的活化 培养细胞，特别是胸腺细胞和神经元细胞，当它们 被诱导进行细胞凋亡; ii）表征活性形式 和ICH-1的体内中间产物; iii）建立 ICH-I与其他死亡基因的关系; iv）鉴定ICH-1 当它被激活的时候。

Programmed cell death (or apoptosis) is of central importance for the development, homeostasis, and in many diseases including cancer, acquired immunodeficiency syndrome, and neurodegenerative disorders. Under genetic control, it occurs through the activation of an intrinsic suicide program as a result of either internal or external signals. ICE/CED-3 cysteine protease family acts autonomously as effectors in dying cells. Nedd-2/Ich-1, a member of this family, was identified that can induce apoptosis in tissue culture cells. My current work suggested that ICH-1 is activated during apoptosis. The overall objective of this proposal is to characterize the functional role of ICH-1 in apoptosis,and its activation mechanism. Specific aims include: i) to examine ICH-1 activation in primary tissue culture cells, especially thymocytes and neuronal cells, when they are induced to undergo apoptosis; ii) to characterize the active form and intermediate products of ICH-1 in vivo; iii) to establish the relationship of ICH-I with other death genes; iv) to identify ICH-1 targets when it is activated.