Transcriptional Induction of pim-1 Protein Kinase Gene Expression by Interferon γ and Posttranscriptional Effects on Costimulation With Steel Factor

• Published in: Blood 1995-06, Vol.85 (12), p.3494-3502
• Main Authors: Yip-Schneider, Michele T., Horie, Masato, Broxmeyer, Hal E.
• Format: Article
• Language: English
• Subjects: Base Sequence; Binding Sites - genetics; Drug Synergism; Gene Expression - drug effects; Hematopoietic Cell Growth Factors - pharmacology; Humans; Interferon-gamma - pharmacology; Leukemia - metabolism; Molecular Sequence Data; Promoter Regions, Genetic - genetics; Protein-Serine-Threonine Kinases - biosynthesis; Protein-Serine-Threonine Kinases - genetics; Proto-Oncogene Proteins - biosynthesis; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins c-pim-1; Recombinant Proteins; RNA, Messenger - biosynthesis; Stem Cell Factor; Transcription, Genetic - drug effects; Tumor Cells, Cultured
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V85.12.3494.bloodjournal85123494

Steel factor (SLF) synergizes with interferon γ (IFNγ) to stimulate proliferation of the human factor-dependent cell line M07e. We examined the effects of IFNγ 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. IFNγ alone, but not SLF, stimulated expression of pim-1 RNA and protein in M07e cells; compared with IFNγ alone, costimulation with IFNγ and SLF resulted in a twofold to threefold increase in pim-1 message and protein expression, correlating with synergistic effects on cell proliferation. Both IFNγ and IFNγ/ SLF induced pim-1 mRNA in the absence of de novo protein synthesis. Nuclear run-on assays showed that, although IFNγ alone increased the rate of pim-1 gene transcription, costimulation with IFNγ 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 IFNγ-responsive element within the 5' flanking region of the pim-1 gene that could confer IFNγ responsiveness on a heterologous promoter was identified. This sequence, designated PMGAS, formed a specific complex with Stat (signal transducers and activators of transcription) 1α (the p91 sub-unit of the transcription factor ISGF3 [interferon-stimulated gene factor 3]) in IFNγ-treated cell extracts, suggesting that the transcriptional effects of IFNγ on pim-1 expression may be mediated by Stat 1α.