Study of molecular mechanism of apoptosis using Drosophila melanogaster ectopical expressing ICE

细胞凋亡是一种重要的自我破坏机制，参与多种生物现象，包括形态发生和维持组织内环境的稳定。细胞凋亡不仅是生物学领域的一个重要主题，而且在医学领域也是一个重要的主题，因为细胞凋亡的失调会导致多种疾病，如癌症和神经退行性疾病。尽管已知细胞凋亡是由半胱氨酸蛋白酶家族(最初称为ICE家族)介导的，但细胞凋亡的分子基础仍不清楚，尤其是caspase下游的信号转导是如何进行的。为了对caspase下游的信号转导途径有一些了解，我们选择了一个果蝇的遗传系统。我们已经建立了几个果蝇系，其中人类ICE(或caspase-1)异位表达，导致形态异常或致死。从这些品系开始，我们用EMS进行随机诱变，获得了许多绕过异常的突变体。通过进行遗传作图，我们在三条染色体上发现了几个明显新的基因，它们与细胞凋亡有关。我们从这些遗传分析中获得的信息为我们能够从分子上克隆这些明显有趣的基因提供了坚实的基础。

Apoptosis is an important self-destruction mechanism involved in a variety of biological phenomena including morphogenesis and maintenance of tissue homeostasis. Apoptosis is an important theme not only in biology but also in medical field because dysregulation of apoptosis leads to various diseases such as cancer and neurodegenerative diseases. Although apoptosis is known to be mediated by a unique family of cysteine proteases, called caspase family (originally ICE family), the molecular basis of apoptosis is still largely unknown, particularly how signal transduction downstream of caspases proceeds. To obtain some insights in signal transduction pathway downstream of caspases, we have chosen a genetical system with Drosophila. We have established several lines of Drosophila in which human ICE (or caspase-1) is ectopically expressed, resulting in morphological abnormalities or lethality. Starting with these lines, we have obtained many mutants after random mutagenization with EMS, that bypass the abnormalities. By carrying out genetic mapping, we have identified several apparently novel genes in three chromosomes, that are involved in apoptotic cell death. The information we have obtained from these genetical analyses provides a solid basis from which we are able to molecularly clone these apparently interesting genes.