CPP32 ACTIVATION DURING DOLICHYL PHOSPHATE-INDUCED APOPTOSIS IN U937 LEUKEMIA-CELLS

Treatment of U937 cells with dolichyl phosphate led to an increase in the activity of the ICE family protease CPP32, accompanied with cleava ge of pre-CPP32 to generate p17, Peptide inhibitors YVAD-cmk and Z-Asp -CH2-DCB (specific to ICE) and DEVD-CHO (specific to CPP32) blocked th e dolichyl phosphate-induced apoptosis, The dolichyl phosphate-induced increase of CPP32 activity was inhibited by adenylate cyclase inhibit ors, SQ 22536 and 2',5'-dideoxyadenosine. Dolichyl phosphate caused a transient increase of intracellular cAMP concentration, The results su ggest that modulation of cAMP synthesis due to the stimulation of aden ylate cyclase by dolichyl phosphate plays a critical role in CPP32 act ivation and apoptosis. (C) 1997 Federation of European Biochemical Soc ieties.