The apoptosis-inducing activity of the two protein phosphatase inhibitors,tautomycin and thyrsiferyl 23-acetate, is not due to the inhibition of protein phosphatases PP1 and PP2A (review)

Thyrsiferyl 23-acetate (TF-23A) has been shown to potently and specifically inhibit PP2A. TF-23A also induced a rapid cell death in various leukemic T - and B-cell lines. The TF-23A induced cell death with a typical apoptotic process. TF-23A and its several analogous compounds showed apoptosis-induci ng activity. However, only TF-23A out of these compounds showed an inhibito ry activity for PP2A. These results suggest that a portion of TF-23A involv ed in induction of apoptosis is different from that involved in the PP2A in hibition. Then, the effects of tautomycin and its derivatives on PPI and PP 2A and their apoptosis-inducing activity were examined. The C-22-C-26 moiet y was essential for inhibition of protein phosphatase activity, whereas the C-1-C-18 moiety was essential for induction of apoptosis. Therefore, diffe rent moieties of tautomycin are involved in protein phosphatase inhibition and induction of apoptosis. From these results, it was concluded that the b iological effects of phosphatase inhibitors are not necessarily induced by the inhibition of PP1 and PP2A but through other different molecular mechan isms which remain to be elucidated.