Transcriptional regulation of the heat shock protein genes by STAT family transcription factors.
We have previously demonstrated that interleukin-6 (IL-6) increases the levels of the heat shock protein 90 (Hsp90) and activates the Hsp90beta promoter via the IL-6-activated transcription factors NF-IL6 and STAT-3. In addition, interferon-gamma (IFN-gamma) treatment increases the levels of Hsp70 and Hsp90 and also enhances the activity of the Hsp70 and Hsp90beta promoters with these effects being dependent on activation of the STAT-1 transcription factor by IFN-gamma. The effect of IL-6/STAT-3 and IFN-gamma/STAT-1 was mediated via a short region of the Hsp70/Hsp90 promoters, which also mediates the effects of NF-IL6. This region also contains a binding site for the stress-activated transcription factor HSF-1. Furthermore, STAT-1 and HSF-1 interact with one another via a protein-protein interaction and produce a strong activation of transcription. In contrast, STAT-3 and HSF-1 antagonize one another and reduce the activation of both the Hsp70 and Hsp90 promoters. Thus, STAT-1 or STAT-3 activation alone or together results in the activation of Hsp promoters. However, STAT-1 or STAT-3 interact differently with HSF-1 to regulate Hsp promoter activity. These results indicate that STATs are able to moduate the Hsp70 and Hsp90 gene promoters and that these transcription factors are likely to play a very important role in Hsp gene activation by nonstressful stimuli and the integration of these responses with the stress response of these genes.
Stephanou
A
A
Department of Molecular Pathology, Windyer Institute of Medical Sciences, University College London, UK.
Latchman
D S
DS
D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D015850:Interleukin-6; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D007371:Interferon-gamma