NUCLEAR FACTOR OF ACTIVATED T-CELLS (NFAT) IS A POSSIBLE TARGET FOR DEXAMETHASONE IN THYMOCYTE APOPTOSIS

Cell death plays a critical role in the generation of an effective imm une system. During maturation T lymphocytes are generated, censored an d eliminated in the thymus. These events an temporally associated with developmental changes in the levels of transcription factors includin g NFAT. The NFAT transcription factor (nuclear factor of activated T c ells) is implicated in the regulation of T-lymphocyte proliferation an d transcriptional activation of genes encoding lymphokines. It has bee n demonstrated that discontinuities in the inducibility of NFAT and AP -1 transcription factors occur during transition of immature thymocyte s into cortical thymocytes which are eliminated by apoptosis. To under stand the molecular basis of these developmental intrathymic changes, we studied DNA-binding activities of transcription factors during dexa methasone-induced apoptosis of immature thymocytes. We observed a spec ific loss of NFAT DNA-binding activity after dexamethasone treatment: It correlated with a selective disappearance of one out of two AP-1 co mplexes. Our data suggest that NFAT complex is a possible target in de xamethasone-induced apoptosis. (C) 1997 Academic Press Limited.