Analysis of genes that are implicated in glucocorticoid-induced apoptosis

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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.