WORTMANNIN ENHANCES CPP32-LIKE ACTIVITY DURING NEURONAL DIFFERENTIATION OF P19 EMBRYONAL CARCINOMA-CELLS INDUCED BY RETINOIC ACID

P19EC cells undergoes apoptosis during neuronal differentiation induce d by retinoic acid. Two CPP32-like proteases, CPP32 and Mch-3, are exp ressed in untreated and retinoic acid-treated P19 EC cells. CPP32-like activity is remarkably increased in apoptosis during neuronal differe ntiation of P19 EC cells. Inhibition of CPP32-like proteases prevents apoptosis, suggesting that activation of CPP32-like proteases play cen tral roles in the apoptosis during neuronal differentiation of P19 EC cells. Wortmannin, PI-3K inhibitor, enhances the CPP32-like activity o f the retinoic acid-treated P19 EC cells. PI-3K may be involved in the apoptosis during neuronal differentiation as negative regulator. (C) 1997 Academic Press.