TitleTranscriptional induction of pim-1 protein kinase gene expression by interferon gamma and posttranscriptional effects on costimulation with steel factor.
Publication TypeJournal Article
Year of Publication1995
AuthorsYip-Schneider MT, Horie M, Broxmeyer HE
Date Published1995 Jun 15
KeywordsBase Sequence, Binding Sites, Drug Synergism, Gene Expression, Hematopoietic Cell Growth Factors, Humans, Interferon-gamma, Leukemia, Molecular Sequence Data, Promoter Regions, Genetic, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-pim-1, Recombinant Proteins, RNA, Messenger, Stem Cell Factor, Transcription, Genetic, Tumor Cells, Cultured

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.

Alternate JournalBlood
PubMed ID7540064
Grant ListR01 HL46549 / HL / NHLBI NIH HHS / United States
R01 HL49202 / HL / NHLBI NIH HHS / United States
R37 CA36464 / CA / NCI NIH HHS / United States