Kv. Voelkerding et al., POSTTRANSCRIPTIONAL REGULATION OF THE P53 TUMOR-SUPPRESSOR GENE DURING GROWTH-INDUCTION OF HUMAN PERIPHERAL-BLOOD MONONUCLEAR-CELLS, Oncogene, 10(3), 1995, pp. 515-521
Regulation of p53 gene expression at the posttranscriptional level was
investigated during growth induction of human peripheral blood mononu
clear cells (PBMCs). Freshly isolated PBMCs, which are in the G(0) pha
se of the cell cycle, were shown to express low levels of p53 mRNA tha
t was rapidly degraded with a half life of Ih. The rapid decay of p53
mRNA in quiescent PBMCs was dependent on global protein synthesis as t
reatment with cycloheximide resulted in stabilization of the p53 messa
ge. PBMCs were stimulated to enter the cell cycle by treatment with a
combination of the mitogenic lectin phytohemagglutinin (PHA) and phorb
ol ester (TPA). Progressive stabilization of the p53 message occurred
in PBMCs during growth induction. By 24 h of incubation in the presenc
e of PHA and TPA, the half life of p53 mRNA was 6 h and p53 mRNA stead
y state levels were increased 4.5 to 5.0-fold. p53 protein was not det
ected in quiescent PBMCs, but was readily detected in PBMCs stimulated
for 24 h with PHA and TPA. Stabilization of p53 mRNA was observed in
PBMCs treated with either PHA or TPA, but to a lesser degree than when
PKA and TPA were used as co-stimulants. These results indicate that d
ifferential degradation of p53 messenger RNA occurs in quiescent vs mi
togen stimulated PBMCs and suggest that post-transcriptional regulatio
n importantly contributes to increased p53 mRNA steady state levels as
PBMCs enter the cell cycle.