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 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.
Centre for Cellular and Molecular Biology, Hyderabad, India.
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Radha
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Sudhakar
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Swarup
D000818:Animals; D017209:Apoptosis; D061945:Caspase Inhibitors; D002467:Cell Nucleus / Q000473:pathology; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D061945:Caspase Inhibitors; D007527:Isoenzymes; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; D017027:Protein Tyrosine Phosphatases