APOPTOSIS INDUCTION BY INHIBITORS OF SER THR PHOSPHATASE-1 AND PHOSPHATASE-2A IS ASSOCIATED WITH TRANSGLUTAMINASE ACTIVATION IN 2 DIFFERENTHUMAN EPITHELIAL TUMOR LINES/

Two epithelial tumour lines, HeLa and KB, were treated with okadaic ac id and calyculin A, specific inhibitors of Ser/Thr phosphatases (PP), esp. PP1 and PP2A, Morphological criteria, analysis of DNA fragmentati on and studies of membrane integrity revealed that both agents concent ration- and time-dependently induced apoptosis at nanomolar concentrat ions which in. these cells was associated with the stimulation of a tr ansglutaminase activity, Since a non-functional derivative of okadaic acid did not affect cell viability apoptosis was apparently related to the inhibition of PP1 and PP2A. Membrane damage marker activity was d elayed by at least 24 h when compared to nuclear alterations. (C) 1997 Federation of European Biochemical Societies.