Azam Sonish, Drobetsky Elliot, Ramotar Dindial
University of Montreal, Guy-Bernier Research Center, 5415 de l'Assomption, Montreal, Quebec, Canada.
Apoptosis. 2007 Jul;12(7):1243-55. doi: 10.1007/s10495-006-0050-8.
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.
PTPA具有肽基脯氨酰异构酶活性，最初作为一种刺激丝氨酸/苏氨酸磷酸酶PP2A微弱磷酸酪氨酸磷酸酶活性的蛋白质被分离出来。在此我们表明，PTPA的瞬时过表达在哺乳动物细胞中以时间依赖性方式导致细胞死亡。过量产生PTPA的细胞表现出凋亡的特征，包括染色质浓缩、细胞膜起泡、膜联蛋白V阳性染色、Bad去磷酸化以及半胱天冬酶-3裂解。用PP2A抑制剂冈田酸处理细胞并不能阻止Bad的去磷酸化或PTPA诱导的凋亡，这表明PTPA不太可能通过PP2A介导其促凋亡作用。此外，我们没有发现p53或丝裂原活化蛋白激酶参与的证据。我们的数据揭示了PTPA在凋亡过程中潜在的新作用。
