Analysis of genes that are implicated in glucocorticoid-induced apoptosis

糖皮质激素（GC）用于治疗白血病或淋巴瘤，因为GC诱导某些类型的淋巴细胞凋亡。然而，GC介导细胞凋亡的机制尚不清楚。本研究利用共聚焦显微镜对GC诱导的细胞凋亡相关的Bcl-2家族蛋白和caspase进行了亚细胞定位分析，在为期两年的研究中，我们得到了以下结果.我们已经鉴定了BH 3-only Bcl-2家族成员的新成员Rad 9，其结合并共定位于Bc 1 -2并促进凋亡。由于人和酵母Rad 9的BH 3区域是保守的，推测单细胞生物如酵母可能具有凋亡调控基因的原型. Bax是Bcl-2家族中的一个促凋亡基因，其启动子区含有4个E-box序列，这些序列可能是c-myc的结合位点。我们已经证明c-myc可以通过与bax启动子中的E-box元件结合来诱导细胞凋亡.使用绿色荧光蛋白作为标签，我们已经深入分析了八个乳腺癌相关的半胱天冬酶的亚细胞定位。大多数caspase成员主要定位于细胞质中。相比之下，caspase-2主要是核caspase。值得注意的是，caspase-8和-10的前结构域形成了引人注目的丝状结构，不与任何已知的细胞器或纤维共定位。

Glucocorticoid (GC) is used for the treatment of leukemias or lymphomas because GC induces apoptosis in certain types of lymphocytes. However, the mechanism of how GC mediates apoptosis in unknown. In this research, we analyzed the subcellular localizations of some of the Bc1-2 family of proteins and caspases implicated in GC-induced apoptosis, using con focal microscopes, During the period of two years we got the results as follows.1. We have identified novel member of BH3-only Bcl-2 family member, Rad9, that binds to and colocalizes with Bc1-2 and promotes apoptosis.2. Since BH3 region of human and yeast Rad9 is conserved, it is speculated that unicellular organisms such as yeast may have prototypes of apoptosis-regulating genes.3. Bax is a proapoptotic member of Bcl-2 family, and the bax promoter contains four E-box sequences that are known to be potential c-myc binding sites. We have shown that c-myc can induce apoptosis through binding to the E-box elements ih bax promoter.4. Using green fluorescent protein as a tag, we have intensively analyzed subcellular localizations of eight apoptosis-related caspases. Most caspase members localized mainly in the cytoplasm. In contrast, caspase-2 was primarily a nuclear caspase. Remarkably, prodomain of caspase-8 and -10 formed striking filamentous structures that did not colocalize with any known organelles or fibers.