A nuclear protein tyrosine phosphatase induces shortening of G1 phase and increase in c-Myc protein level

PTP-S2 is a ubiquitously expressed nuclear protein tyrosine phosphatase whi ch shows increased expression upon mitogenic stimulation in a variety of ce lls in vitro and in vivo. In order to understand the role of this enzyme in cell cycle progression, tetracycline-regulated HeLa clones expressing PTP- S2 were isolated and characterized. Tetracycline-controlled expression of P TP-S2 increased the rate of cell proliferation. An analysis of the distribu tion of cells in various phases of the cell cycle in an exponentially growi ng cell population showed that there was a large decrease in the percentage of cells in G1 phase in a PTP-S2-expressing population of cells compared t o nonexpressing cells. This decrease in the percentage of cells in G1 was d ependent on the level of PTP-S2 expression. There was a corresponding incre ase in the percentage of cells in G2/M but no significant increase in the p ercentage of cells in S phase. An analysis of the time course of cell cycle progression after release from double thymidine block showed that the dura tion of G1 phase was significantly shortened in cells induced to express ex ogenous PTP-S2. However, the duration of S phase was not significantly alte red and the duration of G2 phase was increased to some extent. Induction of PTP-S2 expression was associated with an increase in c-Myc protein levels, although the c-Myc mRNA level was not changed. Our results suggest that ov erexpression of PTP-S2 promotes progression of cells through G1 to S phase and is associated with increased level of c-Myc protein through a posttrans criptional mechanism. (C) 2001 Academic Press.