Signal transducer and activator of transcription-1 and heat shock factor-1 interact and activate the transcription of the Hsp-70 and Hsp-90beta gene promoters.
We have previously demonstrated that interleukin-6 (IL-6) increases the levels of the heat shock protein 90 (Hsp-90) and activates the Hsp-90beta promoter via the IL-6-activated transcription factors NF-IL6 and signal transducer and activator of transcription-3 (STAT-3). Here, we show that interferon-gamma (IFN-gamma) treatment increases the levels of Hsp-70 and Hsp-90 ... and also enhances the activity of the Hsp-70 and Hsp-90beta promoters with these effects being dependent on activation of the STAT-1 transcription factor by IFN-gamma. These effects were not seen in a STAT-1-deficient cell line, indicating that IFN-gamma modulates Hsp induction via a STAT-1-dependent pathway. The effect of IFN-gamma/STAT-1 was mediated via a short region of the Hsp-70/Hsp-90 promoters, which also mediates the effects of NF-IL6 and STAT-3 and can bind STAT-1. This region also contains a binding site for the stress-activated transcription factor HSF-1. We show that STAT-1 and HSF-1 interact with one another via a protein-protein interaction and produce a strong activation of transcription, which is in contrast to our previous finding that STAT-3 and HSF-1 antagonize one another. To our knowledge this is the first report of HSF-1 interacting directly via a protein-protein interaction with another transcription factor. Such protein-protein interactions and the binding of a number of different stress and cytokine-activated transcription factors to a short region of the Hsp-90 and Hsp-70 gene promoters are likely to play a very important role in Hsp gene activation by non-stressful stimuli and the integration of these responses with the stress response of these genes.
Mesh Terms:
Binding Sites, DNA-Binding Proteins, Gene Expression Regulation, HSP70 Heat-Shock Proteins, HSP90 Heat-Shock Proteins, Heat-Shock Proteins, Humans, Interferon-gamma, Interleukin-6, Promoter Regions, Genetic, STAT1 Transcription Factor, STAT3 Transcription Factor, Signal Transduction, Trans-Activators, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Transfection, Tumor Cells, Cultured
Binding Sites, DNA-Binding Proteins, Gene Expression Regulation, HSP70 Heat-Shock Proteins, HSP90 Heat-Shock Proteins, Heat-Shock Proteins, Humans, Interferon-gamma, Interleukin-6, Promoter Regions, Genetic, STAT1 Transcription Factor, STAT3 Transcription Factor, Signal Transduction, Trans-Activators, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Transfection, Tumor Cells, Cultured
J. Biol. Chem.
Date: Jan. 15, 1999
PubMed ID: 9880553
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