Induction of p53 dependent apoptosis upon overexpression of a nuclear protein tyrosine phosphatase

Two ubiquitously expressed protein tyrosine phosphatases, PTP-S2 and PTP-S4 (also known as TC45 and TC48, respectively), are alternately spliced produ cts of the same gene. Overexpression of PTP-S2 be transient transfection in duced chromatin condensation and nuclear fragmentation, typical of apoptosi s. Expression of PTP-S4 resulted in a much loner number of cells with apopt otic phenotype, PTP-S2 induced apoptosis in MCF7 and A549 human tumor cell lines which are p53 positive but not in HeLa and SW620 cells which are p53 negative. Apoptosis induced by PTP-S2 in MCF7 cells nas inhibited by cotran sfection with mutant p53 (Arg-273 --> His) but not by wild type p53, PTP-S2 induced apoptosis was inhibited by antiapoptotic protein Bc12 and certain inhibitors of caspases. These results suggest that the nuclear tyrosine pho sphatase PTP-S2 induces p53 dependent, serum starvation independent and cas pase mediated apoptosis. (C) 1999 Federation of European Biochemical Societ ies.