title: Overexpression of the cis/trans isomerase PTPA triggers caspase 3-dependent apoptosis.
abstract: PTPA, which possesses a peptidyl prolyl isomerase activity, was initially isolated as a protein that stimulates the weak phosphotyrosyl phosphatase activity of the Ser/Thr phosphatase PP2A. Here we show that transient overexpression of PTPA leads to cell death in a time-dependent manner in mammalian cells. PTPA-overproducing cells manifest hallmarks of apoptosis including chromatin condensation, membrane blebbing, positive staining with annexin V, dephosphorylation of Bad, and caspase-3 cleavage. Incubation of cells with the PP2A inhibitor okadaic acid does not prevent either dephosphorylation of Bad or PTPA-induced apoptosis, indicating that PTPA is unlikely to mediate its proapoptotic effect via PP2A. Moreover, we find no evidence for the involvement of either p53 or MAP kinases. Our data reveal a potential novel role for PTPA in the apoptotic process.
authors.affiliation: University of Montreal, Guy-Bernier Research Center, 5415 de l'Assomption, Montreal, Quebec, Canada.
authors.forename: Sonish
authors.initials: S
authors.lastname: Azam
authors.forename: Elliot
authors.initials: E
authors.lastname: Drobetsky
authors.forename: Dindial
authors.initials: D
authors.lastname: Ramotar
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019319:Okadaic Acid / Q000378:metabolism; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000378:metabolism*
chemical_list: D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D051025:bcl-Associated Death Protein; D019319:Okadaic Acid; D020928:Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases; D053148:Caspase 3; D019696:Peptidylprolyl Isomerase