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Transcriptional induction of pim-1 protein kinase gene expression by
interferon gamma and posttranscriptional effects on costimulation with
steel factor
MT Yip-Schneider, M Horie and HE Broxmeyer
Department of Medicine (Hematology/Oncology), Indiana University School of
Medicine, Indianapolis 46202-5121, USA.
Steel factor (SLF) synergizes with interferon gamma (IFN gamma) to
stimulate proliferation of the human factor-dependent cell line MO7e. We
examined the effects of IFN gamma and SLF treatment, alone or in
combination, on the expression of a 33-kD cytoplasmic protein
serine/threonine kinase designated pim-1 whose expression has been closely
associated with proliferation induced by related myeloid cytokines. IFN
gamma alone, but not SLF, stimulated expression of pim-1 RNA and protein in
MO7e cells; compared with IFN gamma alone, costimulation with IFN gamma and
SLF resulted in a twofold to threefold increase in pim-1 message and
protein expression, correlating with synergistic effects on cell
proliferation. Both IFN gamma and IFN gamma/SLF induced pim-1 mRNA in the
absence of de novo protein synthesis. Nuclear run-on assays showed that,
although IFN gamma alone increased the rate of pim-1 gene transcription,
costimulation with IFN gamma and SLF did not further potentiate this
effect; however, the stability of pim-1 message was significantly enhanced
in the presence of both cytokines. An IFN gamma-responsive element within
the 5' flanking region of the pim-1 gene that could confer IFN gamma
responsiveness on a heterologous promoter was identified. This sequence,
designated PMGAS, formed a specific complex with Stat (signal transducers
and activators of transcription) 1 alpha (the p91 subunit of the
transcription factor ISGF3 [interferon-stimulated gene factor 3]) in IFN
gamma-treated cell extracts, suggesting that the transcriptional effects of
IFN gamma on pim-1 expression may be mediated by Stat 1 alpha.
Volume 85,
Issue 12,
pp. 3494-3502,
06/15/1995
Copyright © 1995 by The American Society of Hematology
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