U. Ganapati et al., A nuclear protein tyrosine phosphatase induces shortening of G1 phase and increase in c-Myc protein level, EXP CELL RE, 265(1), 2001, pp. 1-10
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.