REQUIREMENT FOR THE ORPHAN STEROID-RECEPTOR NUR77 IN APOPTOSIS OF T-CELL HYBRIDOMAS

APOPTOSIS is a phenomenon observed during development of many cell typ es in many organisms. It is an internal, programmed cell death charact erized by DNA fragmentation into nucleosome-size pieces1-3. Anti-CD3-i nduced apoptosis in T-cell hybridomas and immature thymocytes requires new gene transcription and may be related to negative selection durin g T-cell development4-6. Using subtractive hybridization, we isolated a complementary DNA clone encoding the orphan steroid receptor Nur77 ( refs 7-9). It shows different patterns of messenger RNA induction betw een apoptotic and stimulated T cells. We report here the use of gel sh ift analysis to demonstrate that the Nur77 protein is present at high levels in apoptotic T-cell hybridomas and apoptotic thymocytes, but no t in growing T cells or stimulated splenocytes. A Nur77 dominant negat ive protected T-cell hybridomas from activation-induced apoptosis. Hen ce Nur77 is necessary for induced apoptosis in T-cell hybridomas.