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

Abstract

Two ubiquitously expressed protein tyrosine phosphatases, PTP-S2 and PTP-S4 (also known as TC⁴⁵ and TC⁴⁸, respectively), are alternately spliced products of the same gene. Overexpression of PTP-S2 by transient transfection induced chromatin condensation and nuclear fragmentation, typical of apoptosis. Expression of PTP-S4 resulted in a much lower number of cells with apoptotic 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 was inhibited by cotransfection with mutant p⁵³ (Arg-273→ His) but not by wild type p⁵³. PTP-S2 induced apoptosis was inhibited by antiapoptotic protein Bcl2 and certain inhibitors of caspases. These results suggest that the nuclear tyrosine phosphatase PTP-S2 induces p⁵³ dependent, serum starvation independent and caspase mediated apoptosis.