ACTIVATION OF C-JUN N-TERMINAL KINASE ANTAGONIZES AN ANTI-APOPTOTIC ACTION OF BCL-2

Bcl-2 is an intracellular membrane-associated protein that prevents ce ll death induced by a variety of apoptotic stimuli. A mechanism by whi ch Bcl-2 exerts an anti-cell death effect is, however, not fully under stood, In the present study, Bcl-2 suppressed cell death of N18TG neur oglioma cells caused by various apoptotic stresses, including etoposid e, staurosporine, anisomycin, and ultraviolet irradiation. Concomitant ly, Bcl-2 disrupted a signaling cascade to the c-Jun N-terminal kinase activation induced by the apoptotic stresses. Bcl-2 also prevented th e etoposide-induced stimulation of MEKK1. Furthermore, overexpression of c-Jun N-terminal kinase antagonized the death-protective function o f Bcl-2. These data suggest that suppression of the c-Jun N-terminal k inase signaling pathway may be critical for Bcl-2 action.