Myeloid growth factor(s) regulation of ornithine decarboxylase: effects of
antiproliferative signals interferon-gamma and cAMP
WL Farrar and A Harel-Bellan
Laboratory of Molecular Immunoregulation, National Cancer Institute,
Frederick, MD 21701-1013.
Colony-stimulating factors (CSFs) stimulate the activation and steady-
state mRNA accumulation of an important regulatory enzyme for
macromolecular synthesis, ornithine decarboxylase (ODC). Cloned murine
CSF-dependent cell lines exhibited a rapid activation of ODC enzyme
activity, detectable within ten minutes of stimulations with either
interleukin-3 (IL-3), GM-CSF, or G-CSF. This early phase of enzyme
activation did not require early protein or mRNA synthesis. The subsequent
protracted rise in ODC activity occurring four to six hours after CSF
treatment was dependent on increases in steady-state ODC mRNA accumulation
and de novo protein synthesis. CSF, therefore, modulates both
posttranslational activation of preexisting ODC and stabilization and
accumulation of ODC mRNA. Antiproliferative signals, such as cAMP or
interferon-gamma (IFN-gamma), effectively inhibited the CSF-directed
increase in steady-state ODC mRNA. Cotreatment of the murine NSF 60.8 cell
line with IFN-gamma and GM-CSF decreased steady-state ODC mRNA greater than
80% as compared with GM-CSF-treated cells alone. IFN treatment did not
cause any appreciable destabilization of mature ODC mRNA, suggesting that
its major effect may be at the level of ODC mRNA transcription or
posttranscriptional processing. These data indicate that the ODC
gene-protein system is an important molecular locus of the effects of
myeloid proliferative and antiproliferation signals.
Volume 73,
Issue 6,
pp. 1468-1475,
05/01/1989
Copyright © 1989 by The American Society of Hematology
